Abstract: The need for standard nomenclature in human genetics was recognised as early as the 1960s, and in 1979 full guidelines for human gene nomenclature were presented at the Edinburgh Human Genome Meeting (HGM) and subsequently published (Shows et al. 1979). The current Chair of the Human Gene Nomenclature Committee, Sue Povey, was elected at the HGM meeting in Heidelberg in 1996. Since then, under the auspices of the international Human Genome Organisations and with the acronym HGNC, we continue to strike a compromise between the convenience and simplicity required for the everyday use of human gene nomenclature and the need for adequate definition of the concepts involved. Numerical identifiers are satisfactory for computers, but when humans need to talk about a gene they prefer to use a name. Increasingly journals are requesting approved gene nomenclature before publication, although more standardisation in this respect would make a significant contribution to the annotation of the human genome (Povey et al. 1997; White et al. 1998). A recent analysis of networks of human genes from 10 million MedLine records illustrates the ingenuity currently required to extract information from the literature (Jenssen et al. 2001). The committee has grown from a single force (Dr Phyllis J. McAlpine) to the equivalent of five professional full-time staff, and operates through the Chair with key policy advice from an International Advisory Committee (IAC, http://www.gene.ucl.ac.uk/nomenclature/IAC.shtml). We also use a team of specialist advisors who provide support on specific gene family nomenclature issues (http://www.gene.ucl.ac.uk/nomenclature/advisors.html). Regular nomenclature workshops are held, frequently to coincide with the annual meeting of the American Society of Human Genetics (ASHG) and the HGM, to ensure that we are approving gene names in line with the needs of the scientific community. Guidelines for human gene nomenclature were last published in 1997 (White et al. 1977) and are also available online. New guidelines will be published in 2002 and a draft version can be inspected at http://www.gene.ucl.ac.uk/nomenclature/guidelines/draft _2001.html. For details of previous and future workshops see http://www.gene.ucl.ac.uk/nomenclature/workshops.html.

Abstract: The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes. Can the draft human genome sequences help us to define the role of these elements more closely?

Abstract: Do we need another review series now we have Nature Review Genetics, Trends in Genetics, and all the current opinion journals? Does anybody have time to read them now? Must we have another high impact journal almost every month? The answer depends as much on the reader's taste as on the way the dish is served. In this regard the annual reviews series has always been unique because of its consistent high quality and broad scope. The editors of the new Annual Review of Genomics and Human Genetics aim to cover these fields in the broadest sense and this they do. This means that while few will read this book from cover to cover, there certainly is something to savour here for everybody. In this first issue for instance, there is a fascinating account by James Crow of his personal experience with human genetics as it developed from its early beginnings with the chromosome maps of the Sturtevant and Morgan labs working on Drosophila. Crow takes us back in time so that we can experience what great skills and determination it took to make those early important discoveries. It is enlightening to see cytogenetics described as `pitiful' in the first half of the last century. But what joy it is to read about discoveries that might have been made but weren't. As Crow says: `some were overlooked, others were simply regarded as uninteresting'. There is a lesson here for all of us. Surely there must be things out there even now to discover which are not recognized because we cannot see beyond our own fixed beliefs? There is much more in this 580-page first volume. Many chapters will appeal to clinical geneticists and those working in diagnostic settings. Scholarly accounts of the genetics of trinucleotide repeat diseases, disorders of iron metabolism, Williams syndrome, newborn screening, and public concern about genetics, are examples of this. On the other hand, fundamental aspects of genetics and genomics are included also, such as estimating allele age, gene family evolution, methods for large scale analysis of sequence variation, or bioinformatic tools. Clearly, this new genomics and human genetics volume is much more appealing to human geneticists than the annual review of genetics which has been on the shelves of many human genetics department's libraries. In short: there is something here for everybody. This new series of high quality reviews can compete with the best in the field.

Abstract: Caenorhabditis elegans populations in which each gene on chromosome I is blocked in turn by RNAi have been grown and phenotypically screened.

Abstract: 1. Canid phylogeny and the origin of the domestic dog 2. Experimental studies of early canid domestication 3. Genetic diversity and phylogenetic relationships of dog breeds 4. Molecular genetics of coat colour, texture and length 5. Mendelian traits in the dog 6. Immunogenetics 7. Genetic aspects of orthopaedic disorders in the dog 8. Genetics of cancer in dogs 9. Genetics of neurological disease in the dog 10. Genetics of eye disorders in the dog 11. Cytogenetics and chromosome maps 12. Canine genomics 13. Genetics of canine behavioural disorders 14. Biology of reproduction and modern reproductive technology 15. Developmental genetics 16. Genetics of morphological traits 17. Olfactory genetics 18. Pedigree analysis, genotype testing and genetic counselling 19. Genetics of quantitative traits and improvement of dog breeds 20. Complex traits 21. Canine model in medical genetics 22. Genetic aspects of performance in working dogs 23. Genetic nomenclature.

Abstract: Despite the recent synthesis of developmental genetics and evolutionary biology, current theories of adaptation are still strictly phenomenological and do not yet consider the implications of how phenotypes are constructed from genotypes. Given the ubiquity of regulatory genetic pathways in developmental processes, we contend that study of the population genetics of these pathways should become a major research program. We discuss the role divergence in regulatory developmental genetic pathways may play in speciation, focusing on our theoretical and computational investigations. We also discuss the population genetics of molecular co-option, arguing that mutations of large effect are not needed for co-option. We offer a prospectus for future research, arguing for a new synthesis of the population genetics of development.

Abstract: The publication of a draft sequence of 90% of the human genome 1 2 heralds an exciting era in human genetics research. In the past 20 years, efforts have focused on mapping and cloning the genes for about 1000 human genetic disorders. This has led to the development of comprehensive services for prenatal diagnosis, carrier testing, and presymptomatic testing of mendelian disorders such as cystic fibrosis and the muscular dystrophies.3 Although this progress has been important to families affected by these diseases, it has had a limited effect on public health. All this could change if knowledge of 2.9 gigabases of the human genome sequence allows us to identify susceptibility genes for common diseases such as diabetes, asthma, and cancer. It may also lead to the identification of genetic variants that define a patient's response to a particular drug. If the promise of the genome sequence is even partially fulfilled, the next decade will see genetics spreading rapidly beyond the confines of specialist centres to impact on the diagnosis and management of common disorders in primary care. #### Summary points Genetic factors contribute substantially to the risk of developing many common diseases Susceptibility genes for common disorders are being sought by genome scans and association studies in large patient cohorts The publication of the sequence of the human genome and the discovery of millions of single nucleotide DNA polymorphisms have enhanced the prospects for identifying complex disease genes Knowledge of such genes would permit identification of individuals at risk of particular diseases, improved preventive medicine, and tailoring of treatment to specific genetic profiles and disease subtypes Single nucleotide polymorphism genotyping is likely to become part of the routine management of some common diseases within the next decade This article is based primarily on reviews in Nature , Nature Genetics , Science , …

Abstract: A comparative study based on four fully sequenced eukaryotic genomes has revealed profound differences in the sets of transcription factors used by plants, fungi and animals.

Abstract: The number of genes predicted for the Caenorhabditis elegans genome is remarkably high: approximately 20,000, if both protein-coding and RNA-coding genes are counted. This article discusses possible explanations for such a high value.

Abstract: The molecular defect in the human disease dyskeratosis congenita is a reduction in function of telomerase. This discovery provides a direct test of the importance of this enzyme in ageing and cancer.

Abstract: Some forms of testicular germ cell tumors (TGCTs) arise from primordial germ cells (PGCs) during fetal development. In both humans and mice, genetic control of susceptibility is complex, involving both Mendelian and polygenic factors. Identification and characterization of TGCT genes will provide insight not only into the basis for inherited susceptibility, but also into the genetic control of the development of the PGC lineage. Recent work has revealed the identity of several susceptibility genes that are inherited as Mendelian traits, the chromosomal location of yet-to-be identified TGCT susceptibility genes, as well as clues to the nature of developmental pathways involved in tumorigenesis. In this review we summarize current understanding of the biology and genetics of TGCTs in mice and discuss the relevance of this work to testicular cancer in humans.

Abstract: The goal of modern human genetics is to correlate genes with disease or, more specifically, relate genetic variation to phenotypic variation. Although this correlation is usually straightforward in the Mendelian disorders, it has proved to be much more difficult to find in the common diseases because they appear to be more complex, likely involving an interplay among multiple genes and between genes and the environment. Although the strategy of linkage mapping of families was very successful when it was applied to the rare monogenic diseases, few common diseases have been mapped to statistical significance. Many investigators are now abandoning linkage analysis altogether and are moving to a candidate gene case-control strategy. In this article, we describe a genealogic approach to mapping human disease genes and provide three examples of how we have used it to map common diseases to statistical significance. We focus on a simple population with little historic migration and use a computerized genealogy database to increase the number of patients who can be compared with other affected relatives through high-density microsatellite genotyping. The genealogy helps determine which phenotypic classification is inherited and therefore possible to map. It may represent a more efficient strategy than candidate gene case-control studies for determination of what alleles or haplotypes are shared by patients in a population. We suggest that the genetics community not give up on linkage analysis, nor should it assume that the common diseases are too complex to map.

Abstract: An INRA equine genomic BAC library was screened by PCR using 24 primer sets developed for the 30UTR of EST clones from a 60-day horse embryo cDNA library [Brandon R., personal communication], 6 CATS primer sets [1] and 1 UM-STS primer set [2]. Clone identity was con¢rmed by cycle sequencing on an Applied Biosystem's Prism Genetic Analyzer. Sequences were compared by BLAST searches to sequences in GenBank. Metaphase chromosome preparation and FISH were performed as previously described [3]. Information on the clones including INRA clone ID number, gene symbol, gene name, horse chromosome map position, clone GenBank accession number and the human gene homolog chromosome map position identi¢ed in the OMIM or NCBI databases is presented in Table 1. The locations of the thirty-one horse genes shown in Table 1 are consistent with human^horse homologies as predicted by ZOO^FISH and synteny mapping studies [4,5]. The position of TCRG on ECA4p de¢nes a new homology with HSA7p. The information in this report increases the resolution of the human^horse comparative gene map.

Abstract: In the past 13 years, a new chapter of human genetics, "mitochondrial genetics", has opened up and is becoming increasingly important in differential diagnosis. Although the clinical manifestations of disorders related to mitochondrial DNA (mtDNA) are extremely variable, recent advances in genetic testing aid in the identification of patients. Muscle morphology can give important clues for diagnosis, but histological features alone cannot define a specific disorder. Biochemical analysis may reveal a single enzyme defect, or when multiple activities are affected, suggest an mtDNA mutation. However, definitive diagnosis often requires DNA analysis and documentation of a specific mtDNA abnormality. Disorders associated with mtDNA mutations are associated with a wide variety of syndromes, and owing to the properties and characteristics of mtDNA, these are often transmitted by maternal inheritance. Although therapy for mitochondrial diseases is limited, identification of the molecular defect is important for genetic counseling.

Abstract: Because public heath professionals will increasingly use genetic technologies and information in research, policy and program development, the purpose of the book, as stated in the Preface, was to delineate a framework for the integration of advances in Human Genetics into Public Heath practice. Even though the book was written by many contributors from various disciplines, the editors succeeded in keeping uniformity of the format, and the book represents a definite entity discussing many aspects of the subject. The book is divided in six parts. The first part con­ sists of an overview of the principles of human genetics in public health, and includes the presentation of a framework for the integration of human genetics into public heath that was developed as part of the Center for Disease Control (CDC) strategic plan. The second part relates to public health assessment in genetics, in particular on various issues on surveillance of birth defects and genetic diseases and disorders with a gene­ tic component. The third part of the book is devoted to public health evaluation of genetic testing, such as the quality assessment program for newborn screen­ ing. The last two parts of the book deal with some ethical and social issues, education, and information dissemination. The main part of the book is on developing, im­ plementing, and evaluating population interventions. Although there is one short chapter from the Nether­ lands, and another referring to developing countries, it would have been interesting to add experiences from other countries, in particular from Europe and the WHO program on Human Genetics. I was surprised to see that there are no chapters dedicated to carrier screening programs or to prenatal screening programs. I understand, however, that this was purposeful, as stated on page 69 in a chapter for which one of the editors was an author: ‘‘. . .it is the authors’ views that the goal of Public Health genetic screening programs should not be genotypic prevention, because the decision to undergo prenatal screening diagnosis and to consider pregnancy termination is intensively perso­ nal and should not be influenced by public health goals, professionals agencies or organizations. Although some geneticists have assessed prenatal testing programs on this basis, such goals can have eugenic implications.’’ As a geneticist, I find this approach very disturbing, because the goals of prenatal genetic programs have never included the abortion of abnormal fetuses. The purpose of carrier screening programs is to give the individual or the couple, a choice to decide whether or not to have the test and whether or not to use it during a pregnancy. The programs for carrier detection of hemoglobinopathies in Mediterranean countries and the U.K., or of Tay Sachs disease among Ashkenazi Jews, have been very successful. A lot may be learned from these programs because millions of individuals have been screened and much of the experience gained should be used in future Public Health genetic screen­ ing programs, even if the aims are different. Similarly, the worldwide experience in the programs offering pre­ natal diagnosis for Down syndrome should have been discussed. In each of the six parts of the books there are excel­ lent chapters that give very good summaries of each of the respective subject. These chapters may serve as the basis for teaching relevant courses. It is my feeling that this book should become a reference to students and practitioners not only in the field of Public Health but also in the field of Medical Genetics.

Abstract: Use of the World Wide Web ("the web") and our knowledge of human genetics are both currently expanding rapidly. By allowing swift, universal, and free access to data, the web has already played an important role in human genetics research. It has also begun to change the way that information is shared in clinical genetics and, to a lesser degree, affect how education in human genetics occurs. There are scores of web sites helpful to those interested in either research or clinical aspects of human genetics. The web and related communication technologies should continue to play increasingly important roles in human genetics.

Abstract: Mice are the most commonly used laboratory animals, owing to the availability of large amounts of information on their genetics and biology. As a result, numerous advanced techniques have been developed by using mouse embryos. Studies on murine developmental and reproductive biology are greatly facilitated by short gestation and generation periods of 20 days and approximately 3 months, respectively. Transgenic and knockout mice are of fundamental relevance to mammalian transgenic research. However, in certain areas of reproductive engineering, the murine model is inadequate because of technical difficulties in manipulating unfertilized oocytes. The techniques of microinsemination and nuclear transfer, for example, were successfully implemented in sheep, cows, and rabbits as early as the 1980s (reviewed in First and Prather 1991; Iritani 1991), but their application in mice remained problematic. In 1995, the establishment of a reliable microinjection technique, enabling the transfer of different types of nuclei into mouse oocytes, considerably expanded the field of mouse gamete micromanipulation. Microinsemination also became possible through the use of mature spermatozoa, immature sperm cells (spermatogenic cells) and round spermatids (Ogura et al. 1994; Kimura and Yanagimachi 1995a). Following these early advances, microinsemination and nuclear transfer techniques in the mouse were further developed, to the point that in 1998 normal pups were born after microinsemination with primary spermatocytes, i.e., spermatogenic cells before the first meiotic division (Kimura et al. 1998; Ogura et al. 1998). Similarly, the first murine somatic cell cloning was carried out after nuclear transfer by microinjection with cumulus cells (Wakayama et al. 1998a). Recently, microinseminations with either spermatozoa or spermatogenic cells were used to generate transgenic mice and to propagate infertile mouse strains. Nuclear transfer techniques are expected to increase the efficacy of transgenic/knockout mouse production and enable the conservation of genetically valuable strains of mice. Cytoplasmic transfer, whereby exogenous mitochondrial DNA (mtDNA) is introduced into recipient oocytes/embryos, is another important technique to generate genetic alterations in the mouse. With this technique, heteroplasmic mice with the new phenotype encoded by the introduced mtDNA have been generated to study mitochondrial segregation during development and the mechanisms underlying mitochondrial disease onset (Jenuth et al. 1997; Inoue et al. 2000; Takeda et al. 2000). In this review, we assess the impact of recently established murine reproductive engineering techniques, such as microinsemination, nuclear transfer, and cytoplasmic transfer, on basic research in biology and mouse genetics. Microinsemination