NEWSLETTER No. 36, May 1998
Views and News is our regular feature, devoted to reporting exciting articles published recently in the Societys own whole- or part-owned journals, Genes and Development and Heredity, plus the recently inaugurated Genes and Function. Views and News also reports on articles published in Nature Genetics, the major sponsor of the newsletter, and occasionally its sister journals. Contributions to this column are welcome from any source, including the authors of the articles concerned who will be acknowledged as such. Please confine contributions to around 300 words, and send them by e-mail to: email@example.com or firstname.lastname@example.org (copy dates as advertised on the front page).
Two genes, Pannier and u-shaped, regulate transcription of proneural genes achaete and scute in Drosophila melanogaster
The stereotyped positions of the large sensory bristles, or macrochaetas, of the Drosophila imago, provide a good model system for the study of pattern formation, and the analysis of genetic variants has allowed the identification of specific genes involved in the generation of this pattern. Each bristle organ is unique and develops within the imaginal disc from a single precursor cell, the sensory organ mother cell. Sensory mother cell (SMCs) arise as the result of a series of sequential steps. First, the competence to become a SMC is conferred to groups of cells at defined positions that prefigure the site of each future bristle. These cells are characterized by the localized expression of the proneural genes achaete (ac) and scute (sc), two members of the ac-sc complex (AS-C).
In a recent issue of Genes and Development two papers of international research groups appeared which demonstrate and characterize two genes, Pannier (pnr) and u-shaped (ush) which together regulate the transcription of achaete and scute (Cubadda et al. - Genes and Development 11: 3083-3085, 1997; Haenlin et al. - Genes and Development 11: 3096-3108, 1977).
Viable hypomorphic u-shaped mutants display additional dorsocentral and scutellar bristles that result from overexpression of achaete and scute. By contrast, overexpression of u-shaped causes loss of ac-sc expression and consequently a loss of dorsal bristles. The effects on the dorsocentral bristles appear to be mediated through the enhancer sequences that regulate achaete and scute at this site. The effects of ush mutants are similar to those of a class of dominant alleles of pannier with which they display allele-specific interactions, suggesting that the products of both genes cooperate in the regulation of achaete and scute. A study of the sites at which the dorsocentral bristles arise in mosaic u-shaped nota, suggested that the levels of the u-shaped protein are crucial for the precise positioning of the precursors of these bristles.
Pannier encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein [GATA factors comprise a family of transcription factors that interacts specifically with the (A/T) GATA (A/G) consensus sequence through a highly conserved zinc finger DNA-binding domain.
The papers summarized here show that both wild-type Pannier and the dominant mutant form activate transcription from the heterologous a globin promoter when transfected into chicken embryonic fibroblasts. Furthermore, Pnr and Ush are found to heterodimerize through the amino-terminal zinc finger of Pnr and when associated with Ush, the transcriptional activity of Pnr is lost. In contrast, the mutant Pnr protein with lesions in this finger associates only poorly with Ush and activates transcription even when cotransfected with Ush. These interactions were investigated in vivo by overexpression of the mutant and wild-type proteins. The results suggest an antagonistic effect of Ush and Pnr function and reveal a new mode of regulation of GATA factors during development.
Is Hox gene spatial expression colinearity universal?
During mammalian fetal development, axial structures acquire their specifications through the action of the Hox gene family of transcription factors. There are 39 such genes that are responsible for giving spatially restricted cues in a variety of embryonic derivatives, from the neural tube to the intestinal tract.
The complex coordination of this control is achieved, in part, through a unique property of this gene family; genes are organized along the chromosome in a genomic sequence that reflects their time and place of activation during development. In mammals, there are four Hox clusters (A to D) and within each cluster, Hox genes located at the 3¢ end are activated first and in anterior embryonic domains, whereas genes located at the 5¢ end
are transcribed subsequently and in more caudal areas. The spatial aspect of this intriguing correspondence, or colinearity, was originally described by the Nobel laureate E.B. Lewis in the Drosophila melanogaster bithorax complex (BX-C), which controls the identity of thoracic and abdominal segments. Since then the same pattern of colinearity has been observed in all animals exhibiting an anterior-to-posterior axial polarity. Interestingly, until now no clear exceptions to this rule have been reported. However, in a recent issue of Genes and Development (12: 11-28, 1998) Godwin and Capecchi present some surprising results from an elegant study of murine Hoxc13, a very posterior gene member of the HoxC complex. Unexpectedly, Hoxc13 is expressed in hair follicles throughout the body as well as vibrissae and in the tongue, that is, at locations much more anterior than expected for the genomic position of this gene. Does Hoxc13 violate the code of colinearity?
Denis Duboule, in his perspective article in the same issue (Genes and Development 12: 1-4, 1998), gives an explanation to the results of Godwin and Capecchi which is in accordance with the colinearity paradigm.
What makes the Godwin and Capecchi report of particular interest is that all hair follicles are involved, regardless of their positions along the body axis. Godwin and Capecchi emphasize that such an observation is apparently at odds with the rule of spatial colinearity, which would have predicted an expression of Hoxc13 in caudal hair follicles only. However, according to Duboule, a slightly different view of these results suggests that if a violation of colinearity is observed, it may not be so serious and, most importantly, does not imply a revision of this concept.
The observed, unexpected expression pattern could be best explained by the functional recruitment of this gene, in the course of evolution, for achieving some additional function in hair follicles such as controlling the production of structural proteins, as proposed earlier by Godwin and Capecchi. The close linkage of the keratin-2 complex to the HoxC locus in mouse chromosome 15 may be indicative of how some Hox genes became involved in hair development, through the potential sharing of the hair follicle-specific global regulatory control. The phenotype indicates that proteins involved in hair solidity, such as some high sulfur proteins associated with keratin intermediate filaments, could be under the control of Hoxc13.
One possible reason for the strange observation of Godwin and Capecchi may rely directly upon the mechanistic basis of colinearity. It has been proposed that vertebrate Hox complexes, early in development, are in closed configuration and that the colinear activation of these genes follows their progressive accessibility through a linear opening of the complexes. In such a view, functional recruitment of a Hox gene for an earlier function, for instance, mesoderm induction, would necessitate premature opening of the complex during development; hence the loss of this critical property.
GS Genetical Society or a selection scheme?
To minimise the inbreeding and genetic drift in a small population with M males and F females (sex ratio r=F/M>1), Gowe et al. (Poultry Sci., 38:462-471, 1959) proposed a selection scheme (denoted as GS) in which each male has one son and r daughters, and each female has one daughter and a probability of M/F of contributing one son. GS has been known as minimal inbreeding and considered in both control populations and conserved populations.
For the same purpose, Wang (Heredity: 79:591-599, 1997) have proposed a selection scheme designated WS. Among the r females mated with each male, one is selected at random to contribute one son, another one to contribute two daughters, and the remaining r2 females to contribute one daughter each. They also propose a mating scheme NM, in which F females are divided into M herds of r individuals. Each male mates at random with one of the M1 non-sib herds. The two selection schemes (GS, WS) are combined with random mating (RM) and herd mating (NM) to form four breeding systems. Recurrent equations for the inbreeding coefficient and formulae for effective size are derived for autosomal and sex-linked loci under each of the four breeding systems.
It is shown that both WS and NM could increase the effective size and decrease inbreeding in any generation compared with Gowe et al.s minimal inbreeding scheme. The most efficient breeding system is a combination of WS with NM, which could increase the effective size by as much as 19 per cent for autosomal loci and 50 per cent for sex-linked loci in comparison with the classical breeding system usually utilised in conserved or control populations. Compared with GS, WS invokes a negative covariance between the numbers of male and female offspring per female parent. Compared with RM, NM decreases the variance in contributions from grandparents and more remote parents. Therefore both WS and NM result in an increase in effective size.
Gene-expression screens in vertebrate embryos: more than meets the eye
Identification of gene function is a central problem in modern biology. With the completion of whole-genome sequencing programmes the next challenge will be to assign a function to all genes identified. Important clues towards gene function can be derived from the knowledge of the expression pattern. A novel approach to large-scale expression analysis is to combine screening of cDNAs by in situ hybridisation and partial DNA sequencing, also called "in situ screening". Such screens are currently underway in Xenopus, zebrafish, mouse and Medaca. With gridded cDNA libraries, robotic processing of DNA and RNA probes and automated whole-mount in situ hybridisation, gene expression screening can be largely automated. Processing of hundreds of clones weekly has become routine. Between 10-25% of picked cDNAs are differentially expressed. In the Xenopus screen, 70% of random-picked cDNAs with differential expression represent unique genes. Of over 200 novel Xenopus genes with regionalized expression identified, 30% encode potential developmental regulators by sequence homology. Thus, this type of screen is efficient in identifying novel developmental regulators. Groups of genes with shared, complex expression patterns called "synexpression groups" identify genes with shared function. By identifying synexpression groups, entire molecular pathways may be identified regardless of functional redundancy of individual components. In situ screens may complement systematic mutagenesis in studying gene function in vertebrates on a large scale. They are attractive due to their simplicity and the immediate access to the cloned gene. In situ screening provides insights into embryonic patterning and may allow identification of entire molecular pathways via synexpression groups and thus goes beyond identifying novel developmental regulators. (Genes and Function 1: 229-231, 1997)
Nefarious effects of HIV Nef on T-cell development
Despite intense investigations the mechanism by which the HIV/SIV Nef protein provides its important contribution to the capacity of these viruses to cause AIDS remains incompletely understood. One approach to elucidate this issue has been the development of transgenic mice expressing Nef under T-cell specific or other promoters, and has revealed a number of aberrations in the T-cell repertoire of such animals. Mice expressing a Nef transgene in their thymocytes and T-lymphocytes have a reduced number of mature single-positive (SP; CD4+ or CD8+) T-cells which fail to respond appropriately to T-cell receptor (TCR)-mediated activation. The surface expression of CD4 is also reduced in both SP as well as in the less mature double-positive (DP; CD4+ CD8+) T-cells of these animals resulting from a Nef-induced increase in CD4 endocytosis, a phenomenon well-characterized by work on cell culture models of Nef action. The fall in the CD4+ cell count during the progression of AIDS is, however, not a consequence of downmodulated CD4 surface expression, but rather due to the killing of CD4+ T-cells, and possibly also due to their impaired renewal. Whether modulation of CD4 endocytosis by Nef could be indirectly involved in the latter process (inhibition of T-cell maturation) has not, however, been addressed until now. A recent study on the effects of Nef transgene expression on mouse T-cell development, published in the December 1997 issue of Genes and Function (Vol. 1: 321-335) by Pennington et al., clarifies this issue and also provides other interesting insights into the role of Nef in CD4+ T-lymphopenia and dysfunction in this transgenic model.
Pennington et al. found that a significant decrease in thymic cellularity developed in the transgenic embryos starting at 16 days post coitus, which is approximately 2 days after the CD2-driven Nef transgene was turned on, and coincided with the time when DP T-lymphocytes started to appear in the thymuses of their normal littermates. When the Nef-transgenic mice were crossed into a CD4-/- background, a similar block in T-cell development was also seen, thus clearly indicating that modulation of CD4 surface expression is not involved in this phenomenon. In agreement with previous reports, the SP T-cells (CD4+ as well as CD8+) which were present in decreased numbers in these animals failed to be activated by stimulation via the TCR, but constitutively expressed several surface proteins considered as markers for lymphocyte activation. Again, identical changes were also seen in mice bred on to the CD4-deficient background. Interestingly, when the Nef transgenic animals were bred with mice transgenic for a dominantly active variant of the TCR-associated Src family tyrosine kinase Lck (Lck-F505), an almost complete restoration of the thymic cellularity was observed. The Nef-induced T-cell dysfunction was, however, still in seen in the Nef/Lck-F505 transgenic mice. A number of knock-out mice lines lacking various components of the TCR-signaling complex, such as Lck, also show deficits in their T-lymphocyte development. Thus, a plausible interpretation of the findings by Pennington et al. is that expression of the Nef transgene is preventing a signal from the TCR which is required for T-cells to mature beyond the double-negative stage of development. As noted by Pennington et al., since the T-cell dysfunction in their Nef transgenic mice was much more profound than what has been reported for Lck-/- mice, it is unlikely that inhibition of Lck is, at least alone, responsible for the observed effects of Nef. Identification of the relevant signaling molecule(s) targeted by Nef thus provides an interesting challenge for future investigations.
What do these findings then tell us about the mechanism of CD4+ T-lymphocyte depletion in AIDS? In this regard, the obvious question becomes how well CD2 promoter-targeted Nef expression in the T-cell lineage reflects the role of Nef during natural HIV infection. Unlike Nef expression in such transgenic mice, only a fraction of the patient CD4 T-lymphocytes are infected by HIV, and it is not clear how the less mature double-negative T-cells lacking the CD4 receptor for HIV would become infected at all. Also, most of the current models of AIDS favor an accelerated destruction of CD4 cells rather than their decreased production. Nevertheless, the striking arrest of T-cell maturation in the transgenic mice reported by Pennington et al., provides another good reason to carefully re-examine the question how HIV infection might not only enhance the killing but also affect the maturation and expansion of CD4+ T-lymphocytes.
Mutation detection and typing of polymorphic loci through double-strand conformation analysis
With the elucidation of many genetic loci encoding variants with functional differences, the use of DNA based screening methods has increased dramatically in the last decade. Techniques utilised for the characterisation and identification of genetic polymorphisms include conformational methods such as SSCP (single strand conformation polymorphism) and Heteroduplex Analysis. We have recently described a method, Double Strand Conformation Analysis (DSCA) which improves significantly the resolving power of other conformational methods (Argüello et al. Nature Genetics 18: 192-194, 1998). DSCA utilises a fluorescent labelled locus specific reference (FLR) DNA molecule which is hybridised with locus specific PCR products from the samples to be tested. Because of similarity between the FLR and sample nucleotide sequence, duplexes are formed between the sense and antisense strands of all the DNA molecules present in the mixture. However, as the FLR sense strand is exclusively labelled, only duplexes formed with this strand are identified by a laser detection system after electrophoresis in an automated DNA sequencer. As the detected duplexes have the FLR sense strand in common, the molecular conformation of each duplex generated is in principle unique, as each anti-sense strand is different, therefore duplex mobility is expected to also be unique thus allowing the separation of each allele or variant. Unlike other conformational techniques such as SSCP, where the conformation of the DNA molecules cannot be manipulated, the use of a FLR allows control of duplex conformation as several FLRs can be tested in order to achieve optimal separation of difficult samples. As non-denaturing polyacrylamide gels are utilised, the gels can be re-used up to five times with only a buffer change.
We have applied DSCA for the typing of the most polymorphic genetic loci, the HLA system and also for the identification of mutations within the cystic fibrosis gene. DSCA is a sensitive technique, variant alleles differing by as little as a single nucleotide in fragments as large as 1kb have been identified. DSCA is a sensitive, reproducible method which can be utilised for high throughput screening for the identification of genetic mutations, critical to our understanding of many diseases.
Ann-Margaret Little, J. Rafael Argüello & J. Alejandro Madrigal
Oxytocin and Mammary Gland Development
The conversation of the oxytocin gene in vertebrates and invertebrates suggests that oxytocin (OT) conveys important functions that are not restricted to its milk releasing effect in mammals. It has been postulated to be required also for the initiation and maintenance of parturition, memory, maternal behaviour, and fertility, among others. However, genetically engineered mice deficient in OT are fertile, give birth to normal sized litters, show the same maternal behaviour as wild-type mice, but are unable to nurse their young because of the disruption of the neuroendocrine milk-ejection-reflex (Young et al., J.Neuroendocrinol. 8: 847, 1996). In normal mice, increased amounts of OT are secreted from the posterior pituitary gland into the circulation upon the suckling stimulus of pups. Subsequently, OT induces the contraction of myoepithelial cells surrounding the mammary alveoli, which leads to the ejection of milk. We were able to restore the milk ejection reflex in OT-deficient dams by administrating exogenous doses of OT. In addition, we have tested the hypothesis that OT controls, directly or indirectly, the development of the mammary gland (Wagner et al., Genes and Function 1: 233, 1997). In particular, we examined alveolar proliferation and mammary function in post-partum mice. Our findings demonstrate that the impaired milk release caused by the absence of OT is linked to the repression of the post-partum proliferation and expansion of alveolar structures. Phosphorylated Stat5a, which is a downstream mediator in the prolactin-signalling cascade, was sharply reduced. This suggests that OT-deficient mammary tissue rapidly looses functional differentiation. In addition, rapid programmed cell death is initiated in mammary tissue in post-partum deficient dams, even in the presence of suckling and the continued release of lactogenic hormones such as prolactin into circulation. In contrast, OT is not required for the growth and terminal differentiation of myoepithelial cells and has no measurable effect on the release of lactogenic hormones from the anterior pituitary. Mice deficient in OT therefore serve as an appropriate model to distinguish between the effects of systemic and local factors in the maintenance and programmed cell death of the alveolar compartment of the mammary gland. For more information see our web site at http://mammary.nih.gov.
Mendelian factors affecting correlated traits: A case of chromosome inversion
Although fitness-related effects of chromosome inversions have been found in a number of Drosophila species, the karyotypic effects on the correlation among quantitative traits were largely unexplored. However, polymorphic inversions may be adaptive not only by affecting fitness-related traits considered single, but also by influencing genetic correlations among adaptive traits. One of the reasons for this assumption is simple: the immediate genetic response to selection depends not only on the heritabilities of traits considered single but also on the genetic and phenotypic covariances among all the traits of which the phenotype is composed. Our suspicion is that genetically correlated traits are the most prevalent direct target of selection influencing genetic polymorphisms in nature.
In a recent study (Heredity 79: 585-590), the hypothesis that chromosome inversions affect correlations among size-related traits was examined in the cactophilic species D. buzzatii. Previous work in this species showed that the second-chromosome inversions additively affect body size, a fitness-related trait, and other traits correlated with it (see Heredity 79: 585-590, for the many references). In this work, phenotypic correlations among size-related traits of head, thorax, and wings, were compared between inversion karyotypes (genotypes) within and between populations. No similarity in the phenotypic correlation pattern (Mantel's test) was observed between some karyotypes in a natural population, but the similarity test was highly significant for a same homokaryotype in different populations and/or environments (see also Hereditas 126: 225-231). The results are consistent with the hypothesis that chromosome inversions influence genetic correlations among traits, but whether this effect is due to pleiotropic gene action or gametic disequilibrium of linked genes that affect size-related traits is unknown.
Overall, it was previously demonstrated that the second-chromosome inversions affect fitness-related traits in wild populations of D. buzzatii (Evolution 48: 740-755, Genetics 128: 739-750; J. Evol. Biol. 8: 369-384). Therefore, these chromosome arrangements may influence the genetic correlation among adaptive traits, as suggested in this study (Heredity 79: 585-590). This is exactly what the adaptive basis of the inversion polymorphism implies. Any attempt to understand the processes involved in the maintenance of this polymorphism in the wild will, therefore, require knowing the specific effects of each inversion on the genetic correlation between fitness-related traits.
Fabian M. Norry
Response to Genetic variation at marker loci and in quantitative traits (Newsletter No. 35, p. 19-20)
The last sentence of this article, Still too little is known about the ecology of life history variation in Arabidopsis caught Michael J. Lawrences (School of Biological Sciences, The University of Birmingham) eye. Readers of the Newsletter might possibly be interested in an article he wrote over 20 years ago which attempted to summarise what was then known about variation in natural populations of Arabidopsis. Since this paper was published in a book about various aspects of the Cruciferae, it is not easily accessible and may, for this reason, have been overlooked.
The experiments Dr Lawrence reviewed do not tell us why it is advantageous for populations of A. thaliana to maintain metrical polymorphisms, only that this apparently is the case. We cannot be certain that the genetic variation detected in the laboratory is expressed in the same way in the natural environment of the species. However, the experiments reviewed persuade us that, since the traits he had considered appeared to be subject to selection, despite the effort required, it is worth attempting to identify the physical and biotic factors of the natural environment which maintain these polymorphisms. See: Variations in natural populations of Arabidopsis thaliana (L). Heynh. In The Biology and Chemistry of the Cruciferae. Eds. J.E. Vaughan, A.J. MacLeod & B.M.E. Jones, Academic Press, London, 1976.
The conversion from phenotypic to functional nomenclature can be painful
In recognition of the need for improved dialogue between the scientific community and nomenclature curators, and also for a common genetic language, Nature Genetics Editorial (Vol. 18: 89-90, 1998) requests that authors consult with the appropriate nomenclature committee prior to reporting the discovery of a novel gene. According to the Editorial in cases where a symbol cannot be decided upon before publication, a provisional or temporary symbol can be used. Establishing an approved symbol increases the advantage that this symbol will become permanent. A guide to nomenclature protocol and various nomenclature systems in different organisms can now be found on the Nature Genetics website: http://genetics.nature.com/nomen/ with links to the appropriate databases. Its authors Julia White, Lois Maltais & Dan Nebert point out that additional funding for nomenclature resources is urgently required. Extensive efforts are now being made to standardize nomenclature across species. Also, as Lois Maltais, who co-ordinates the mouse nomenclature database, puts it: the emphasis is no longer on the gene as a single entity, but how groups of genes work together.
In addition, Hester Wain, Joseph Nahmias, Julia White & Sue Povey at the Human Gene Nomenclature Committee are trying to remedy this problem along with the help of geneticists and other scientists in relevant fields of expertise (see in this issue: The Nomenclature Conscience, A personal view page 28).
The human and mouse nomenclature committees encourage investigators in specific fields to set up their own committees. As Julia White (HUGO) points out, there is no point in having a wonderfully elegant system that beautifully reflects phylogenetic relationships, if no one remembers what the symbols are. Nature Genetics Editorial makes a special plea for more specialist advisors: for example, those with expert knowledge of genes associated with the apoptosis-signalling cascade are especially welcome at the present time.
FEGS is the Federation of European Genetical Societies, of which the Genetical Society was a founder member.
The Federation of European Genetical Societies - a retrospective
The first Newsletter of the Genetical Society (No. 1, July 1989) carried a piece by Bryn Bridges announcing our Forward Look. The aim of having a membership of 2,000 by the end of 1993 was optimistic, but the Society has certainly gone a long way down the road of revitalising itself in the way it intended in 1989. The Forward Look was proposed by Bryn Bridges at the November Committee Meeting of 1988 in UCL, and the details were worked out later in the evening in an Italian restaurant somewhere in Bloomsbury. Amongst other things we proposed to forge links with similar societies elsewhere in Europe. This plan followed on from a promise we gave at the International Congress of Genetics (ICG) in Toronto in 1988, when it was announced that we had won the bid to host the next ICG in the UK in August 1993. The process of contacting other societies in Europe was begun by Michael Lawrence, then Senior Secretary, and later continued by myself as his successor.
The establisment of the FEGS took some time, and some effort was needed to squeeze the set-up funds out of DG12. Initial reluctance was overcome by a personal visit to Brussels, and the loosening of the purse strings over a long lunch. A grant of £5,000 (without a formal application !) was secured, and we were able to cover the expenses of twelve Founder Members to meet in the Bonnington Hotel in London over the weekend of March 7/8th 1992 (Austria, Czechoslovakia, France, Germany, Hungary, Italy, Poland, Portugal, Scandinavia, Spain, Switzerland and the UK) . The Genetical Society was represented by Paul Nurse (President), Michael Lawrence (Vice President) and myself; together with Giovanni Romeo, representing the European Society of Human Genetics and Derek Smith as Secretary General of the next ICG. Nature Genetics provided the wine, and we set up the FEGS and drafted its statutes. The big surprise was the discovery that we knew virtually nothing about one anothers societies. It was also evident that the Genetical Society was far and away the largest and best organised of any of the European Societies. This event itself was a conference, as well as a FEGS set-up, and many useful and long-lasting contacts and friendships were made.
The FEGS was formally launched with a ceremony and reception at the ICG in Birmingham on August 19th 1993. Nature Genetics sponsored the reception. At the first business meeting I discovered that I had set my own trap and became the first FEGS President (1993 -1997). Dieter Schweizer (Vienna) was elected Secretary, Walther Traut (Lübeck) accepted the post of Treasurer and Seppo Lakovaara (Finland, Scandinavia) became the Meetings Councillor. What happened next ? We held our first FEGS meeting at the venue of the Genetical Society Spring meeting in Swansea in March 1994, and our second one at the venue of the Swiss USGEB meeting in Zürich in March 1996. At the Swiss meeting we ran a symposium on Transposable Elements, organised by Dieter Schweizer, as well a plenary lecture on Human Gene Therapy by Max Birnstiel. The plenary attracted an audience of more than a thousand.
Later on we initiated the FEGS mini-symposia. The first of these was held at the venue of the Aberystwyth Cell Genetics Group meeting on Physical Mapping of Plant Chromosomes, 9-11 January 1997, and this proved to be a highly successful international event. The second mini-symposium, on Animal Models for Genetic Disease, organised by Roser Gonzalez (President, Spanish Genetical Society) was held at the venue of the 1st meeting of the SEG in Valencia September 1997, and this one also proved highly successful and informative. The formula of holding small local meetings throughout the FEGS constituency works much better that large-scale international conferences. It is also economical in terms of organisation - cuckoo conferencing.
In the meantime, as we say, membership has grown. Including those waiting to join, the FEGS now has 24 member societies, many connected by email. Communication has always been a tussle, but with electronic connections gathering pace this problem should soon be overcome and our aspiration to have good discussion and information exchange amongst member societies could soon be attained - notwithstanding the many different languages and currencies involved.
The FEGS has grown, but its sustaining membership, in terms of who pays their dues to the central administration, remains weak, and will need to be addressed urgently by the new management. The Genetical Society has been generous in its support of the FEGS, including a number of grants to enable established UK Geneticists to undertake visits to countries in eastern Europe to give lectures, to advise on research and to establish collaborations. This scheme, known as EGGS (European Genetics Guest Speakers) was run by myself and attracted a number of sponsors in addition to the Genetical Society.
Sponsorship and the generation of income is the FEGS big nightmare. Unilever has been a regular contributor, and other funds have been obtained from time to time from Promega, Carl Zeiss, Elsevier Science, Nature Genetics and Blackwell, and the FEGS is grateful to these providers. After seven years of involvement, and many pleasurable experiences - mostly in eastern Europe, I hand this monster over to new enthusiasts.
I suppose the high-spot must be the overnight train journey from Warsaw to Vilnius, in 1996. I never knew this before, but the gauge of the track is different in the former Warsaw Pact counties from what it is in the former Soviet Union, and as you pass unknowingly in the dark from Poland into Belarus, en route to Lithuania, they stop the train at the frontier, jack it up and change all the wheels. Its must be the worst way to awake from a deep sleep. The real nightmare starts further down the line though, when a number of menacing looking guys in bright green uniforms, and some nasty looking equipment, wake you for the second time and ask for your passport. Not expecting to be in Belarus anyway, one had no visa, and shortly thereafter no passport either. The passport can only be recovered after getting dressed, disembarking from the train at 5.00 am and paying $50 at the customs office. The train obligingly waits while this official robbery takes place. Alternatively, you can fly from Warsaw to Vilnius, sometimes, if you can cope with seeing the canvas through the rubber on the wheels of the old Russian aircraft.
Such pleasures await my successor as President, Yolanta Maluszynska of the Department of Plant Anatomy and Cytology, Silesian University, Katowice. David Cove will serve as the Genetical Society Council Member and as FEGS Treasurer. Dieter Schweitzer will continue as FEGS Secretary. I will otherwise occupy myself as Dean of science at Aber and become an ordinary member of the Genetical Society again for the first time in the last twelve years.
Professor David Cove as Genetical Society representative
Professor David Cove of Leeds University is the new Genetical Society member on the FEGS council, as well as FEGS Treasurer.
Correction of Professor Coves E-mail address: D.J.Cove@leeds.ac.uk
see also http://www.leeds.ac.uk/biology/research/cove.html):
FEGS Internet FEGS - http://dns.unife.it/geneweb/agi/fegs/html
The award of the Mendel Lectureship to Professor Sir David Hopwood FRS is in recognition of an exceptional research career during which Streptomyces genetics has grown from an outstanding Ph.D. thesis in Cambridge in the mid-1950s into one of the major subjects of microbial genetics world-wide in the 1990s. When the 35-year old Dr Hopwood took up his appointment as Head of Genetics at the relocated John Innes Institute in Norwich in 1968, one paper in 250 submitted to the leading microbiological journals dealt with Streptomyces, but the figure is now about one in 25, a change largely attributable to his influence. At Cambridge, with Whitehouse, and at Glasgow in Pontecorvo's Department, he had already invented systems for genetic analysis of Streptomyces coelicolor A3(2) and obtained a linkage map of more than 100 markers; established the basic features of this strain's morphogenesis; and collected hundreds of morphological mutants that are still a rich resource today. S. coelicolor had been established as the "E. coli" of antibiotic-producing bacteria.
During the next decade, his investigation of S. coelicolor resulted in the discovery of indigenous plasmids, the development of protoplast fusion and transformation, and the initiation of studies of four sets of genes for antibiotic synthesis: achievements marked by his election as an FRS in 1979. In the 1980s, he oversaw the full flowering of cloning in Streptomyces, leading to the first isolation of gene sets for antibiotic production and, famously, the use of these genes to direct hybrid antibiotic production. During the 1990s, these studies have led to the on-going elucidation of the means by which the simple iterative condensation of acetate residues into long chains can generate the vast diversity of polyketide-derived structures found throughout nature. This process forms not only antibiotics and other pharmacologically active compounds, but also flower colours and bacterial specificity factors for symbiosis. Meanwhile, David's interest in general S. coelicolor genetics is undiminished: under his guidance a detailed physical map and collection of ordered cosmids for the chromosome have been prepared and the unexpected linearity of the chromosome has been revealed. The "full Monty" - determination of the complete genome sequence of S. coelicolor - is now in progress at the Sanger Centre, and its completion under David's coordination will be a perfect culmination of the genetic investigations that began with his PhD.
David's outstanding scientific contributions are recorded in about 300 publications. He has been Secretary and President of the Genetical Society, organised a variety of meetings and practical courses, pioneered the publication of the universally used Streptomyces genetics manual (now being rewritten), and received numerous appointments as a University External Examiner. He has been recognised by a string of prizes and honorary memberships of microbiological societies in many countries. Among the awards have been the Royal Society Gabor Medal (1996) and - of particular note in the context of the Mendel Lectureship - the G. J. Mendel Honorary Medal of the Academy of Sciences of the Czech Republic (1996). As an ambassador for British science, particularly microbial genetics, and as an exemplar of bridging the often overstated gap between basic and industrial science, David has been peerless. His Knighthood in 1994 did great credit, both to him and to the Public Honours system.
Mervyn Bibb & Keith Chater
GENETICAL SOCIETY NEWS
Leaving office - reflections on Genetical Society directions - a retrospective
It has been both a privilege and a burden, to have the opportunity of influencing events in an organisation like the Genetical Society - and I hope a good number of you will volunteer for election to the committee so you too can take a turn at this. I served three years on the committee before the President of the day, Paul Nurse, asked me to take on the treasurership from September 1993, allowing an overlap with Mike Merrick, my helpful, efficient and knowledgeable predecessor. The carrot was a full-time Membership Secretary post, to deal with all of you including many money matters and day-to-day running and some of the longer-term tasks such as meeting organisation. The Medical Research Council proved very helpful in providing space and administering the Membership Secretarys post. That is how Jill Hunter, with experience of running a business, dealing with VAT, and, as it turns out, with quite a flair for organising meeting venues, came to work in our Unit in the late summer of 1993. Sadly, she is just about to leave the Genetical Society for pastures new, after making the move successfully to the new treasurer's office at Roslin.
I do not want to give a blow-by-blow account of balancing the books, that was time-consuming and somewhat tedious but trouble-free after the excellent management by my predecessors. What I would like to comment on is the Genetical Societys remit and its duty to members, as I perceive it. Being a seasoned committee member for several years provides a great opportunity to participate in the main business of the Society: planning meetings and then watching you all vote with your feet. As treasurer, it was of course my duty to help plan successful meetings, meaning exciting topics with must-hear speakers. We agonised endlessly to get the blueprint right, which means not becoming too formulaic, but rather serving up a succession of delectable surprises. This ought to be easy, with genetics moving on such a wide front. Genetics has become the tool to dissect so much of biology. There is a wealth of mutants isolated over the years in what are now regarded as classical organisms: E. coli, the yeasts, maize, rice, wheat, latterly Arabidopsis, Caenorhabditis elegans, Drosophila, recently zebrafish, mouse and even man. There are plenty of other organisms, including nasty parasites like malaria which can provide novel insights into development, reproductive strategies, and weird but mechanistically instructive sexual or asexual life cycles. I have always been excited by the vast diversity of survival strategies and now we are beginning to understand so many intimate details - like mating type switching in yeast, or sex determination in nematodes, Drosophila and mice - at the molecular or even nucleotide level, but there are still many mysteries such as the reasons for the evolution of imprinting in mammals. With the advent of the genome projects and proliferation of databases, it has been very exciting to see evolution at work. The most impressive part is how conservative evolution is! Who would have foretold that PAX6, the gene I have been working on as a human geneticist interested in the relatively mild eye phenotype aniridia (absence of the iris), has been around in hydra and C. elegans since before eyes had appeared. PAX6 was then repeatedly co-opted by evolution to make eyes, to very different plans, in insects, jellyfish and vertebrates. The DNA-binding domains remain 80% amino-acid identical from nematode to man, and ectopic expression studies in Drosophila have led to the somewhat exaggerated suggestion that PAX6 is the master control gene for eye development. It has been a revelation that once nature has come up with a good working set of gene interactions to accomplish some task, it does not readily let go its invention, it just modifies and refines, with occasional duplication to allow a little more evolutionary leeway. I suppose Darwin would not have been surprised.
We have tried to reflect the excitement of the times in our meetings and I hope that the Genetical Society will continue to steer a broad course, allowing us to hear about the latest advances in many different processes in a wide variety of creatures. We also need to keep informed about the quantitative aspects of evolution, of population movements, of breeding selection for continuous traits as well as the dissection and identification of the underlying genes. It is instructive that we can contemplate understanding some of the controls gone haywire in cancer by studying cell cycle control in yeast.
Of course, there is no better organism than Homo sapiens to observe the widest spectrum of variation, since we cherish and keep going our variants, so that mankind provides the best genetic model system, so long as we can use other species, phyla and kingdoms to explore gene function experimentally.
Finally, but very importantly, it is the duty of all geneticists, and the Genetical Society collectively, to think deeply about the long term safety of the genetic manipulation techniques made possible by our work. We need to ensure that time is set aside for discussion, using our expert knowledge to assess the scientific, moral, ethical and societal issues that are now constantly in the news.
Veronica van Heyningen
The retirements of both Rosemary Harvey, the Archivist and Elizabeth Atchison, the Curator of the Rare Books have occasioned a number of changes within the John Innes Library. The Archives, History of Genetics Library and the Collection of Rare Botanical Books have been brought together under the direction of the Main Science Library. In February 1997 Elizabeth Stratton was appointed Archivist and Historical Collections Librarian and now manages all the John Innes Foundation Collections.
Elizabeth is a qualified Archivist and obtained her M.A. in Archives and Records Management at University College London in 1994. She completed a series of short term archival contracts at the John Innes Centre in Norwich, Oxfordshire Archives, New College Oxford and King's College, Cambridge. She believes firmly that archival records and historical material exist to enrich and complement the modern context in which we all work.
As Archivist Elizabeth's objective is to manage and promote the Historical Collections as an unique and integrated resource to be used by historians, scientists and the general public alike. During the past year external researchers have pursued their interests in garden design, history of art, book production techniques, the Innes family and the history of JIC, Gregor Mendel, the Potato Genetics Department and the National Rose Collection. Tours of the Collections have also been provided for several groups of local garden and plant enthusiasts, visiting scientists from all over the world, botanical historians and professional librarians.
Exhibitions provide an ideal opportunity to increase awareness and interest in the Historical Collections amongst JIC staff and visitors alike. Topics this year have included displays on "Palms", "the Dahlia", "A tribute to Brian Harrison", "Nuts Illustrated" and "Japanese Botanical Art". An exhibition on the History of Botanical Illustration was also set up in the Rare Book Room in association with the "Fanfare of Flowers" Art Exhibition held in the JIC Lecture Theatre.
Plans to make information about the Historical Collections more widely available include developing the Internet pages and the publication of a general information leaflet. The Botanical Books have already featured in a brief news item on BBC Look East broadcast in November 1997. A preservation programme for the Collections has also been set up. Although the controlled environments in both the Archive Store and the Rare Book Room have effectively preserved the material there are still a number of books which need rebinding or repair and some of the archival material is in a fragile condition.
The name of the 1999 Balfour Lecturer will be announced in the September Newsletter.
The Genetical Society e-mail address database now contains about one-third of the entire membership. However, in order to help us stay in touch with all of our members effectively we need electronic addresses from those of you who have not so far responded. On-line members receive advance information about meetings and other matters requiring urgent attention. Please send a one-line message to the Societys anonymous mail-box:
containing only your real name and institution, e.g. Michael Ashburner, University of Cambridge. Over the course of time, many e-mail addresses change. We can only keep up with changes if you notify us of them! Anyone who thinks that their e-mail address may have changed during the past year can ensure that they remain on the Genetical Society database simply by sending a new, one-line message to us, as above. In addition, the Society has a web-site, currently accessed through the University of Leeds Department of Biology, and maintained by our Education Officer, Alan Radford.
The newsletter is mounted on the web-site shortly after hard-copy publication, and you can also use the web-site to access advance information about Genetical Society meetings, and to download copies of registration forms. The Genetical Society internet address is:
Retiring Treasurer: Veronica van Heyningen
As reported in the December newsletter, Helen Sang has taken over from Veronica van Heyningen as Genetical Society treasurer. Veronica has put in many years of service to the Society, and we are deeply grateful for all her hard work. We all wish her the very best in her future activities. See her retrospective above, page 19.
Jennie Davies, The Genetical Society, Roslin Institute, Roslin, Midlothian EH25 9PS, Tel: 0131 527 4472, Fax: 0131 440 0434, E-mail: Gensoc.Memsec@bbsrc.ac.uk
A special issue of the International Journal of Developmental Biology has just come out, on the Developmental Genetics of Drosophila. Edited by Alain Ghysen, it is dedicated to Antonio Garcia-Bellido, and features articles by many distinguished geneticists on a wide range of topics in the genetics of pattern formation and cell determination. There is a special emphasis on homeotic selector gene function and evolution, and a section is also devoted specifically to the career and achievements of Dr Garcia-Bellido. Genetical Society members can purchase this special issue of the journal at the reduced price of 5.000 Spanish pesetas. Please address your order to the following address, mentioning your Society membership:
Int. J. Dev. Biol. Editorial Office, Dept. Cell Biology, Medical School, University of the Basque Country, 48940 Leioa, Spain, Fax: +34 4464 8966, email: GCPARMA@lg.ehu.es
GENETICAL SOCIETY COMMITTEE MEMBERS 1998/1999
According to the Genetical Society constitution, the agenda for the business meeting should be circulated at least 6 weeks beforehand. The last meeting was at Warwick, on Thursday 2 April 1998. Because we are no longer publishing a February newsletter, the agenda was posted on the Genetical Society website in early February, and all members who wished to attend the business meeting were urged to consult it.
Members of the Society who wish to put forward their names, or those of colleagues, for future election to the Genetical Society committee, should contact the Senior Secretary, Julian Burke (email@example.com). The election takes place at the business meeting held each year at the spring meeting. Ordinary committee members are officially elected to represent the various interest groups in genetics, as specified on the membership application form, but in practice these are very widely interpreted. What counts most is enthusiasm, charisma and breadth of knowledge, to help serve our very diverse membership. Normally, the committee will put forward its own nominees for the positions to be filled, but it is open to all members to propose names.
Report on the Genetical Society Spring Meeting, University of Warwick, 1-3 April 1998
This meeting brought together scientists, physicians and even members of the actuarial and insurance professions; a testament to the future global impact of the genetics of health and disease on society. The focus of the meeting was largely on common diseases, with a particular emphasis on cardiovascular disease, diabetes and obesity, and other conditions that drastically affect society such as mental development, deafness and alcoholism. Talks describing studies on human populations and model systems such as mouse, Drosophila and the nematode worm were presented, which helped illustrate the multidisciplinary nature of the genetic analysis of common diseases and how essential and illuminating the use of models can be - and will be in the future.
Common diseases are characterized by complex interactions between multiple genetic loci, which are most likely to be common DNA variants with low penetrance, and environmental factors. Cardiovascular diseases, such as hypertension, atherosclerosis and thrombosis, exemplify well the relationship between genetic and environmental components. Cambien described associations between gene polymorphisms and lifestyle such as alcohol consumption, smoking and physical exercise, all of which are known to increase disease risk. For example, the association of a TaqI polymorphism in the CETP gene with HDL levels appears to be dependent on alcohol consumption. Polymorphism in the ACE gene has been associated with a wide variety of cardiovascular disease-associated traits, including the association of the ACE D/D genotype with end stage renal failure in polycystic kidney disease. For traits such as autism, behavioral abnormalities, substance abuse and psychiatric disease, thorough and longitudinal records of lifestyle and phenotype parameters will be essential to detect, confirm and understand the associations of common polymorphisms with common diseases. Of course we cannot expect the inheritance of common polymorphisms to be straightforward, as illustrated by Reik and Lalande who discussed the common phenomenon of genomic imprinting: parent of origin effects, which include imprinting as one mechanism, need to be considered in every study whether it be a genome scan or association study. The function of imprinted genes in growth and development, especially neurological development, and also in behavior, is a fertile area of research.
However, the aetiological variants (even) in the ACE gene and its flanking DNA have not yet been defined. This is a major challenge for the genetics of common disease: the definition of common allelic variants with functional effects that can account directly for the marker allele associations observed. It has taken over ten years to pinpoint the aetiological variant at the type 1 diabetes disease susceptibility locus IDDM2 to the minisatellite VNTR in the promoter of the insulin gene (INS) (Bennett). These studies involved linkage mapping, association or linkage disequilibrium mapping and, most informatively, the association of specific haplotypes with disease. Once haplotypes are defined then their associations with disease can be evaluated for their content of alleles or polymorphisms that could have functional effects (on expression or activity of the protein). The cost is that all common polymorphisms must be defined in the associated chromosome region and this requires extensive sequencing studies, large amounts of genotyping and statistical analyses.
How large might associated regions be, particularly if they have been under selection pressure during human history and given that regions of linkage disequilibrium might be much larger that we expected owing to the recent and rapid growth of many European populations? We do not know. Haplotype mapping studies by Farrall suggest that sequences in the 5 region of the ACE gene are not associated with plasma ACE levels, at least, not in the Caucasian population he studied. Yet it is not yet known how far linkage disequilibrium extends in the ACE gene region and thus it remains uncertain where the aetiological variants are located on the common Disease-associated haplotypes in Caucasians - Farrall only studied 8 kb of the relevant chromosome, which included the ACE structural gene. In fact, only about 16 kb of the INS region was studied in detail, leaving open the possibility that other polymorphisms other than the INS VNTR might be aetiologically active in the development of type 1 diabetes in this chromosome region. A vast number of single nucleotide polymorphisms (SNPs) will be required to define the complete haplotypic content of trait-associated chromosome regions and to permit association tagging of each ancestral haplotype segment, where segments, identical-by-descent between unrelated individuals in the population, have been scrambled by ancestral recombination events. It was evident at the meeting (Day, Brookes) that breakthroughs in technology, for SNP detection and typing, will be required to cope with projects that will require millions of genotypes rather than the current 100,000-400,000 genotypes required in whole genome scans using 300-400 polymorphic microsatellites.
Many of the emerging aetiological variants in common disease have, as expected, high frequencies in the general population. A recurring question at the conference concerned the possibility that such common functional polymorphisms might have been selected because they bestowed an advantage during evolution, such as in perinatal survival via growth mechanisms favoring adaptation to famine conditions, in survival of infectious disease (Weatherall) and in other processes such as wound repair (Cambien, Henney). Allelic variants that once improved performance in these aspects of growth and survival may now, in modern, urbanized, well-fed societies predispose to disorders such as cardiovascular disease, obesity, asthma and autoimmunity. Polymorphisms in ACE may also be associated with birth size, providing support for the thrifty genotype hypothesis (Cambien, Polychronakos). Another potential thrifty genotype is the INS VNTR class III/III genotype, which has been associated with birth size (Bennett and Todd).
It is anticipated that genetic information will be important for improving drug therapy, by allowing sub-populations carrying a known genotype to be targeted. Henney illustrated such potential for tailored, targeted drug therapy. Whilst working on matrix metalloproteinase genes he has identified a polymorphism in the stromelysin promoter that is associated with a three-fold increased risk of rapid progression of atherosclerosis. Individuals who carry a 6A allele, present in 50% of the population, show an improved response to the drug prevastatin. The blockbuster cholesterol lowering drugs may only be beneficial in individuals carrying certain CETP genotypes. The emerging field of pharmacogenetics is currently restricted by a lack of technology and poor understanding of the repertoire of common functional polymorphisms in the human and mouse genomes.
One way to identify chromosome regions that carry common aetiological variants is by genome scanning for linkage, as described at the meeting for type 2 diabetes (Bell), autism (Maestrini), obesity (Li), type 1 diabetes (Peterson), alcohol preference (Silver) and multiple sclerosis (Peltonen, Compston). These early scans have provided encouraging results which can be followed up with additional families and scans of linked chromosome regions for allelic association and haplotype content mapping. However, the necessity of working in parallel in animal or lower organism models was a major take-home message, not only to understand gene function but to map new genes involved in homologous traits in humans. This message was most aptly illustrated by the back-to-back talks by Heberlein and Silver, who presented their studies on alcohol preference in fruit flies and in mice. The cAMP pathway of signal transduction is crucial in the response to alcohol in the fly, and it is anticipated that some of the alcoholism genes mapped by Silver in mice will also fall in this pathway. Studies of the genetics of deafness (Brown) and of obesity (Harris) in mice have led directly to human disease genes, and a beginning of an understanding of the biology of the gene products via the analysis of different alleles. The pros and cons of simple knockout mutations where discussed. It is clear that conditional mutations and mutations at specific sites that are not null mutations can provide dramatic insights into function. Current and future mutagenesis programs in mice, and other lower organisms such as flies and worms, will be particularly informative, as will be a complete catalogue of human gene diversity.
Amidst one of the most exciting phases of scientific endeavor, we must, as professionals, ensure the publics understanding of what we are doing and how, and in what time scale, it will benefit those who are ill or those that are genetically predisposed to be ill in the future. Your Human Genetics Advisory Commission (Sir Colin Campbell) needs you!
Simon Bennett & John Todd
In addition to the main symposium, the meeting featured the Balfour Lecture by Colin Stirling, who summarized his pioneering work on the genetics of the secretory pathway in yeast, as well as the award talks by this years Promega Young Geneticists (Stuart Ingleston, Shi Ming Si-Hoe and Anthony Brown). The poster session was a notable success, with over 40 posters, Stephen Clapcott (University of Liverpool) winning the Trends in Genetics student poster prize, for his presentation on QTL mapping of trypanosomiasis-resistance in the mouse. The social programme featured a barn dance, which bore some resemblance to the inebriometer device described by Ulrike Heberlein, a contraption that selects for intoxication-sensitive flies on the basis of their inability to remain upright in a confined space.
With 220 participants, this was one of the most successful Genetical Society conferences of recent years, and thanks are due to scientific organizers John Todd and Simon Bennett, to Jill Hunter, Katariina Juhola and the Warwick hospitality team led by Haidee Hargreaves for the organizational aspects, and to Sue Bougourd, our Sponsorship Officer. The Society is very grateful to all of the sponsors and advertisers (see display ad on page 24) who helped make the meeting possible.
EIGHTH MAMMALIAN GENETICS AND DEVELOPMENT WORKSHOP
Report on the meeting held at the Wellcome Trust Building, London, 19- 21 November 1997
As in previous years, the workshop was extremely well attended. More than 130 participants attended the meeting over the three day period. Of these, 41 were new members. Their names and addresses have been added to the MGDW membership list which now exceeds 400 individuals. Several participants came from Continental Europe (i.e., Belgium, Germany, and Spain). Although contributions were received form laboratories based around the globe (Continental Europe, North America and South Africa), the majority were from United Kingdom based laboratories. Of these, more than a half came form outside the greater London area.
The programme, which consisted of 38 presentations, covered many species and scientific disciplines. Studies ranged across various species, including: 1) chickens to investigate role of the HMG box DNA binding protein (SOX9) in the development of cartilage; 2) mice to investigate a whole range of genetic and developmental processes (e.g., genome imprinting, sex determination, neural tube defects); and 3) man to evaluate genome stability, genetic basis of disease susceptibility as well as aspect of genome imprinting and disease.
In keeping with our overall objectives, the majority of the contributions were presented by junior members of the scientific community. Both the content and standard of presentation were exemplary. There is no doubt the communication skills of our young scientists has increased significantly over the years. For this, they should be applauded.
As last year, the abstracts of the meeting will be published in Genetical Research later this year.
All agreed that the meeting was extremely worthwhile, promoting both useful discussions as well as valuable interactions. With the continuing increase in new membership, as well as the ability to attract participants from abroad, there is no doubting that the Workshop fulfils an extremely valuable niche.
Sponsors: Wellcome Trust, Genetical Society and B&K Universal Group Limited.
Andrew Copp & Dennis Stephenson (workshop organisers)
THE GENETICAL SOCIETY/PROMEGA YOUNG GENETICISTS MEETING
Report on the meeting held in Aberystwyth, Saturday 22 November 1997
The meeting was held in the A14 lecture theatre on the Penglais Campus, starting at 10.30 a.m. There were seven speakers and a plenary lecture. Two of the speakers were from the University Institute of Biological Sciences, two from the nearby Institute of Grassland and environmental Research, two from the University of Swansea and one from the University of Newcastle. The topics were extremely diverse, as shown by the list of titles below, impinging on development, ecology and evolution, amongst other subjects!
The young geneticist speakers were Zoe Phillips, Institute of Biological Sciences, UWA Aberystwyth (Regulation of the transition state in Clostridia), Charlotte Lewis, IGER Aberystwyth (The responses of Lolium temulentum to elevated CO2 and varying irradiance during growth and development), Helene Vanacker, IGER Aberystwyth (The role of antioxidants in leaves and I the leaf apoplast in the hypersensitive response to powdery mildew attack in barley), Anthony Brown, University of Newcastle (Investigation of a low temperature inducible barley promoter), Jonathan Head, Institute of Biological Sciences, UWA Aberystwyth (The molecular nature and cytological consequences of genome expansion), Gareth Jenkins, Centre for Molecular Genetics and Toxicology, University of Swansea (Restriction site mutation analysis of induced DNA mutations) and Jim Harvey, School of Biological Sciences, UW Swansea (Genetic impact of the Sea Empress oil spill).
The speakers were all exceptionally good, both in the substance of their work and in their presentational skills, and the judges found great difficulty in separating the fine shades which distinguished them. The final choice, by a slim margin, went in favour of Anthony Brown from Newcastle. The plenary lecture, on amazing maize, by Dr. Keith Edwards from IACR, Long Ashton, was outstandingly informative and inspirational. The event was greatly enjoyed by the 20 or so participants and the meeting ended at 4.45 p.m.
Reports on the other 1997 Promega meetings at the John Innes Centre in Norwich and at the University of Newcastle-upon-Tyne appeared already in the December 1997 issue of the newsletter, No. 35. Note also the full details of how to participate in the 1998 meetings, which will be held in Glasgow, Sheffield and Oxford: see pages 7-8.
GENES PAST, PRESENT AND FUTURE: CELEBRATING 40 YEARS OF GENETICS AT TRINITY COLLEGE, DUBLIN
Report on the joint TCD/Genetical Society academic meeting at Trinity College Dublin, and the public symposium at the Point Theatre, Dublin, 12-14 March 1998
The Genetics Department at Trinity College Dublin celebrated its 40th anniversary with a series of events in mid-March. Central to these was the official opening by the Taoiseach (Prime Minister) of a new multi-million pound building, the Smurfit Institute of Genetics, which will house the entire Department and give it scope to expand. To mark the occasion we held a two-day academic symposium and a day of lectures for the public.
The joint TCD/Genetical Society academic symposium, "Genes Past Present and Future", took place on Thursday and Friday, 12-13 March in the Edmund Burke Theatre, Trinity College Dublin. There were about 250 registrants. The twelve speakers were a mixture of old friends of the Department (including four external examiners of TCD undergraduates), current collaborators, and local graduates made good. In keeping with the Department's anniversary, the speakers were encouraged to take a 40-year perspective on how their fields had changed in the past and might progress in the future. Masatoshi Nei (Penn State) began his review of Darwinian molecular evolution by mentioning Erwin Schrödinger's book What is Life, which was written in Dublin in 1944 and was based on a series of lectures given at TCD. Schrödinger's book was influential in attracting many physicists to become the first generation of molecular biologists. Paul Sharp (Nottingham) spoke on the evolution of viruses and showed that the earliest isolates of HIV were appearing at about the same time as TCD's Genetics Department. Other speakers on the first day were Sir David Hopwood (East Anglia) on Streptomyces genetics and natural product biosynthesis; David Sherratt (Oxford) on recombination, replication and chromosome segregation in bacteria; John Atkins (Utah) on the genetic code and programmed frameshifting; and André Goffeau (Louvain) on the yeast genome and how having the complete genome sequence has changed the way yeast molecular biology research is done. Following the official opening of the building, Friday's speakers were Bill Brammar (Leicester) on the eukaryotic cell membrane; Sir Walter Bodmer (ICRF and Oxford University) on the genetics of colorectal cancer; Michael Ashburner (Cambridge University and EMBL-EBI) on Drosophila genomics, genetics and the FlyBase project; Mario Capecchi (Utah) on Hox gene mutations and their effect on the bodyplan, Cahir O'Kane (Cambridge) on the genetics of Drosophila brains; and Michael Conneally (Indiana) on the genetics behind common complex disorders such as alcoholism. If a common thread existed across all the talks, it was that genomics (a word coined only a decade ago) is now centre stage to almost all genetics research.
On Saturday 14 March the public symposium "Genetics and Society in the 21st Century" was held in the Point Theatre, Dublin. This was an all-day event running from 10 a.m. to 5.30 p.m. with seven speakers. The decision to hold the symposium in the Point (Dublin's largest theatre) instead of in TCD was made when it became apparent that there was considerable interest from the general public. About 1500 people attended; the admission charge was £3.50 for the public (with free admission to TCD students and people attending the academic symposium on the previous days). The speakers and their titles were Ian Wilmut (Roslin Institute, Edinburgh) Cloning in biology and medicine; Sir John Maddox (Editor Emeritus of Nature) "Does modern genetics imply eugenics?"; Baroness Mary Warnock Genetics and philosophy: new thoughts for old subjects; Rockne Harmon (Chief Deputy Attorney, Alameda County, California) After OJ Simpson: forensic DNA in the 21st century; Martina McGloughlin (Director of Biotechnology, University of California, Davis). A quarter century of genetic engineering: the US public experience has been positive; Borge Diderichsen (Novo Nordisk, Copenhagen) Genetic engineering: science and industry serving society; Roger Beachy (Scripps Institute, San Diego) Agricultural biotechnology and food production.
Genetic engineering has been in the headlines in Ireland throughout early 1998, particularly with regard to the introduction of genetically modified foods and Monsanto's trials of "Roundup Ready" (glyphosate-resistant) sugarbeet on some Irish farms. This interest was reflected in the high turnout from the public, assisted by extensive advance media coverage. The Irish Times newspaper (one of the sponsors of the meeting) ran a half-page interview with Baroness Warnock during the preceding week, as well as several smaller interviews and a fullpage report on the day's event on the following Monday. Ian Wilmut was interviewed on the Late Late Show (the leading television chat show) the night before the symposium, and Martina McGloughlin was a guest on a radio phone-in programme.
When banner-carrying protesters in fancy dress turned up outside the theatre at 8 a.m. we realised that the day might be eventful. The police intercepted a lorryload of sugarbeet that was parked suspiciously nearby. There was some criticism of the selection of speakers in advance of the symposium, with the Irish organisation Genetic Concern describing it as unbalanced and a "showcase for apologists for the biotechnology industry". In the end the symposium was picketed by about 50 protesters from several organisations. Ms Nuala Ahern, the Green Party MEP for Leinster, addressed the audience immediately before the two question-and-answer sessions with the speakers, and spoke passionately and critically. Most of the questions from the floor were also hostile to the biotechnology industry. Ian Wilmut and Roger Beachy, in particular, were graceful under fire. It was clear that there were two separate groups of people in the audience, pro- and anti- biotechnology, and it is unlikely that many people's minds were changed by the symposium. Nevertheless we at TCD felt that it was good to put our heads above the parapet and contribute to the debate.
The Genetical Society has been recognised by the Inland Revenue as a learned society. Members can claim tax relief against their subscription. They should quote List 3 Fees and Subscriptions paid to Professional Bodies and Learned Societies.
THE NOMENCLATURE CONSCIENCE
A personal view by Hester Wain, Joseph Nahmias, Julia White and Sue Povey
So, after years of years of painstaking research you've finally achieved your goal and cloned your gene: The obvious next step is publication. But wait!. What is that little voice of conscience from the corner of the lab whispering?...."Nomenclature?". At this point many scientists, turn away and begin writing their long awaited paper, sure in the knowledge that no one else could possibly have thought of the name that they are about to bestow on their creation. So when this breathtaking new discovery takes its first steps into the world it is identified with a name which all will know and remember.
At this stage, I am afraid, reality must intrude, as so many genes are named by their discoverers in this way, that often the names are far from unique and impart little information as to the true character or function of the gene in question. We, at the Human Gene Nomenclature Committee are trying to remedy this problem along with the help of scientists in their relevant fields of expertise. With the development of cloning technologies the number of genes discovered each year is increasing and thus the problem of naming genes will not go away but is in fact the driving force behind the need to ensure each one is uniquely identified.
A new gene, like a new baby deserves a name which is fitting and will identify it for the rest of its existence by its uniqueness. If every one was called Graham Brown, life would get very complicated as no one would know to whom you were referring and what their relationship was to anyone else. As with a new baby, a new human gene needs to be registered and this should be done with the Human Gene Nomenclature Committee as soon as possible, at http://www.gene.ucl.ac.uk/nomenclature/
It is at this stage that the name and symbol for the gene is discussed with the author and a suitable unique symbol, representing the gene name is agreed upon. Gene names are very special and we encourage authors to choose a name which conveys something of the structure, function or familial relationships of the gene in question. Once approval of the new gene symbol is granted your gene may go out into the world, safe in the knowledge that no other gene will have the same approved symbol and that it is now part of a growing database of approved genes which is used by many, including Nature Genetics, Genomics, OMIM (Online Mendelian inheritance in man), The Mouse Database (MGD) and SWISS-PROT, to name but a few.
A list of the current approved gene symbols is available at http://www.gene.ucl.ac.uk/nomenclature/genew.shtml Recent additions to these include:
ATQ1: antiquitin 1
TGFBR1: transforming growth factor, beta receptor I
PDS: Pendred syndrome
KCNQ2: potassium voltage-gated channel, KQT-like subfamily, member 2
MYPT1: myosin phosphatase, target subunit 1
For more information about any existing or new human gene nomenclature, or for information about finding gene nomenclature guidelines in other species, please do feel free to contact us, as with your help we can ensure the validity of the approved gene symbols. Guidelines for Human Gene Nomenclature (1997) are also available from http://www.gene.ucl.ac.uk/nomenclature/guidelines.html. o let your conscience be your guide, register your gene and get an approved gene symbol from Julia, Joseph, Hester (Tel: 44-171-504-5027, Fax: 44-171-387-3496) or Sue, the Human Gene Nomenclature Committee
Hester Wain, Joseph Nahmias, Julia White and Sue Povey
IS ENGLISH A UNIVERSAL LANGUAGE FOR THE TERMINOLOGY OF GENETIC ENGINEERING?
In all natural sciences the main medium of international communication is English. It is the language of original publications as well as of congresses. However, in order to spread knowledge and new research results over a wider public, the use of other national languages is necessary. Of course, those national languages must - to some extent - adopt the terminology of the respective science, but not necessarily in the English form itself (as it very often seems to be in oral everyday communication in academic circles). In my doctoral thesis Etymologie und Anpassung gentechnologischer Termini in schwedischen, dänischen und deutschen populärwissenschaftlichen Texten (English title: Etymology and adaptation of terms of genetic engineering in Swedish, Danish and German popularized texts, Vaasa 1997) I investigated the terminology in popularized texts dealing with genetic engineering. Above all I was interested in the question: Where do the genetical terms come from?
The starting point was a corpus of about 40.000 words, contained in 20 articles taken from journals like the Swedish Forskning och Framsteg. From these articles I isolated the terms (with the help of a geneticist and a biologist) and analyzed them using linguistic methods (above all those of morphology and historical linguistics) as well as statistics.
Well, where do the terms of my corpus come from? The main sources are: heritage (terms built of native material, for example in Swedish sträng for DNA-sträng DNA strand), classical languages (Latin/Greek, as in Swedish population population), German (for the Scandinavian languages, as in Swedish art species), French (as in Swedish barriär in korsningsbarriär barrier to crossing) and only rather seldom: English (as in Swedish DNA DNA, in spite of Swedish syra acid, compare German DNS with S for Säure acid; or - better - as in Danish genetic engineering). About one quarter of all terms belonged to the heritage, approximately 60% were classical (half Latin and half Greek!), 5% German (in the Scandinavian texts), only some percent French and even less English.
More detailed investigations showed that very many classical (and also other foreign) terms first came into German which transmitted them to the Scandinavian languages. This is a result of very long lasting German cultural influences on Scandinavia. Another, even bigger part of originally classical material (approximately one quarter of all terms) can be found in terms which do not have any equivalents in Latin or Greek (as in Swedish plasmid plasmid or protoplast protoplast). Such terms are normally the newest ones. They were created in an English-dominated research milieu, but do not look English at all. On the contrary: Everyone thinks them to be classical. They have almost the same form in all languages and are therefore real internationalisms. Genuine English words are - as already mentioned - very seldom. Scientific English itself - like all important languages - still depends very much on the classical roots. The formation of new terms from classical material is nothing specifically English, each of the three languages which I have investigated (Swedish, Danish and German) has already been doing this for a long time.
Of course I have also compared the three languages Swedish, Danish and German. I have found that the Swedish popularized texts show a much higher portion of native elements than the Danish texts. This seems to correspond to the opinion that the Swedish try to take care of their language more than the Danish. The Swedish texts showed also a slightly higher portion of German and French elements, while the Danish ones had more English terms and more internationalisms (like described above). The German texts had approximately as many native elements as the Swedish ones (which is amazing, because German is a more important language and has influenced the Scandinavian languages very much) and more classical terms.
With regard to the adaptation of foreign terms (their form in a special language) I could find out that for the Scandinavian languages (especially for Danish) the German pattern (and not the English one) is decisive. This has also to do with the long German influence on Scandinavia. The English influence has been comparatively very short, too short and not deep enough to determine the form of the Scandinavian terms.
The future of the language for scientific purposes - at least concerning their popularized version - seems to be like its past: classical and very little English. The international language of science forms its terms by using classical elements, and so does English, too. The Swedish example shows that it is even possible to have a maximum of native elements in it, without the danger that society could be informed insufficiently.
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Last updated 7 May 1998