Abstract: A brief history of human genetics and genomics is provided, comparing recent progress in those fields with that in pharmacogenetics and pharmacogenomics, which are subsets of genetics and genomics, respectively. Sequencing of the entire human genome, the mapping of common haplotypes of single-nucleotide polymorphisms (SNPs), and cost-effective genotyping technologies leading to genome-wide association (GWA) studies - have combined convincingly in the past several years to demonstrate the requirements needed to separate true associations from the plethora of false positives. While research in human genetics has moved from monogenic to oligogenic to complex diseases, its pharmacogenetics branch has followed, usually a few years behind. The continuous discoveries, even today, of new surprises about our genome cause us to question reviews declaring that "personalized medicine is almost here" or that "individualized drug therapy will soon be a reality." As summarized herein, numerous reasons exist to show that an "unequivocal genotype" or even an "unequivocal phenotype" is virtually impossible to achieve in current limited-size studies of human populations. This problem (of insufficiently stringent criteria) leads to a decrease in statistical power and, consequently, equivocal interpretation of most genotype-phenotype association studies. It remains unclear whether personalized medicine or individualized drug therapy will ever be achievable by means of DNA testing alone.

Abstract: Although genes have long been appreciated to play a critical role in determining the risk for pervasive developmental disorders, the specific transcripts contributing to autism spectrum disorders (ASD) have been quite difficult to characterize. However, recent findings are now providing the first insights into the molecular mechanisms underlying these syndromes and have begun to shed light on the allelic architecture of ASD. In this article, we address what is known about the relative contributions of various types of genetic variation to ASD, consider the obstacles facing gene discovery in this complex disorder, and evaluate the common methodologies employed to address these issues, including linkage, molecular and array-based cytogenetics, and association strategies. We review the current literature, highlighting recent findings implicating both rare mutations and common genetic polymorphisms in the etiology of autism. Finally, we describe key advances in genomic technologies that are transforming all areas of human genetics and consider both the opportunities and challenges for autism research posed by these rapid changes.

Abstract: An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, tracking, hunting, and so forth are likely to be controlled, at least in part, at the genetic level. Recent studies in canine genetics suggest that small numbers of genes control major morphologic phenotypes. By extension, we hypothesize that at least some canine behaviors will also be controlled by small numbers of genes that can be readily mapped. In this review, we describe our current understanding of a representative subset of canine behaviors, as well as approaches for phenotyping, genome-wide scans, and data analysis. Finally, we discuss the applicability of studies of canine behavior to human genetics.

Abstract: The NHGRI's Advanced DNA Sequencing Technology program is spearheading the development of platforms that will bring routine whole-genome sequencing closer to reality.

Abstract: The specific skipping of an exon, induced by antisense oligonucleotides (AON) during splicing, has shown to be a promising therapeutic approach for Duchenne muscular dystrophy (DMD) patients. As different mutations require skipping of different exons, this approach is mutation dependent. The skipping of an entire stretch of exons (e.g. exons 45 to 55) has recently been suggested as an approach applicable to larger groups of patients. However, this multiexon skipping approach is technically challenging. The levels of intended multiexon skips are typically low and highly variable, and may be dependent on the order of intron removal. We hypothesized that the splicing order might favor the induction of multiexon 45–55 skipping. We here tested the feasibility of inducing multiexon 45–55 in control and patient muscle cell cultures using various AON cocktails. In all experiments, the exon 45–55 skip frequencies were minimal and comparable to those observed in untreated cells. We conclude that current state of the art does not sufficiently support clinical development of multiexon skipping for DMD.

Abstract: The landscape of human genetics has changed remarkably in a relatively short space of time. The field has progressed from comparatively small studies of rare genetic diseases to vast consortia based efforts that target the inherited components of common complex diseases and which typically involve thousands of individual samples. In particular, genome wide association studies have become possible as a result of a new generation of genotyping platforms. At the time of writing, these have led to the discovery of more than 150 novel susceptibility loci across a broad spectrum of diseases, a few in genes with high biological plausibility but the majority in others that had not been considered candidates. Here, we provide an overview of the field of complex disease genetics pertaining to mapping by association and consider the many pitfalls and caveats that have arisen.

Abstract: Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents’ homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants’ conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child’s condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients’ understandings of illness causality and inheritance.

Abstract: In 2007, five whole genome-wide association studies were published on the genetics of type 2 diabetes mellitus (T2DM), followed by the discovery of 11 genes consistently associated with T2DM. This breakthrough provided the first glimpses of a complete picture of the disease's genetic complexity. Currently, we are only beginning to understand how DNA methylation, histone acetylation, and deacetylation may introduce epigenetic changes throughout one's lifetime. Such changes may influence age-related modifications in gene-expression that contribute to age-related diseases. In the future, the possibility of whole-genome DNA methylation studies may elucidate the extent of these epigenetic effects. This article reviews genes that have recently been determined to be associated with T2DM.

Abstract: PREFACE INTRODUCTION PART 1: THE FOUNDATIONS OF HUMAN AND MEDICAL GENETICS 1. Before Mendel 2. Mendelism and Human Inherited Disorders 3. The Rise of Classical Genetics 4. The Beginnings of Molecular Biology PART 2: HUMAN GENETICS 5. Human Chromosomes 6. Human Biochemical Genetics 7. The Human Gene Map 8. Genes, Populations and Human Inherited Disorders 9. Human Genetics as a Scientific Discipline PART 3: MEDICAL GENETICS 10. From Human to Medical Genetics 11. The Elements of Medical Genetics 12. Medical Genetics, the Laboratory Basis 13. Human Molecular Genetics 14. The Management, Therapy and Prevention of Genetic Disease PART 4: GENETICS AND SOCIETY 15. Eugenics 16. The Tragedy of Russian Genetics 17. Medical Genetics, the Ethical Dimension PART 5: CONCLUSION AND APPENDICES 18. History in the Making APPENDIX I: GENERAL SOURCES APPENDIX II: TIMELINE REFERENCES

Abstract: Genetic diseases are recognized to be one of the major categories of human disease. Traditionally genetic diseases are subdivided into chromosomal (numerical or structural aberrations), monogenic or Mendelian diseases, multifactorial/polygenic complex diseases and mitochondrial genetic disorders. A large proportion of these conditions occur sporadically. With the advent of newer molecular techniques, a number of new disorders and dysmorphic syndromes are delineated in detail. Some of these conditions do not conform to the conventional inheritance patterns and mechanisms are often complex and unique. Examples include submicroscopic microdeletions or microduplications, trinucleotide repeat disorders, epigenetic disorders due to genomic imprinting, defective transcription or translation due to abnormal RNA patterning and pathogenic association with single nucleotide polymorphisms and copy number variations. Among these several apparently monogenic disorders result from non-allelic homologous recombination associated with the presence of low copy number repeats on either side of the critical locus or gene cluster. The term ‘disorders of genome architecture’ is alternatively used to highlight these disorders, for example Charcot-Marie-Tooth type IA, Smith-Magenis syndrome, Neurofibromatosis type 1 and many more with an assigned OMIM number. Many of these so called genomic disorders occur sporadically resulting from largely non-recurrent de novo genomic rearrangements. Locus-specific mutation rates for genomic rearrangements appear to be two to four times greater than nucleotide-specific rates for base substitutions. Recent studies on several disease-associated recombination hotspots in male-germ cells indicate an excess of genomic rearrangements resulting in microduplications that are clinically underdiagnosed compared to microdeletion syndromes. Widespread application of high-resolution genome analyses may offer to detect more sporadic phenotypes resulting from genomic rearrangements involving de novo copy number variation.

Abstract: The results of two published genome sequences from marine diatoms provide basic insights into how these remarkable organisms evolved to become one of the most successful groups of eukaryotic algae in the contemporary ocean.

Abstract: Education of health professionals about genetics is essential to the integration of genetics into mainstream health care, but there are a number of associated challenges. By virtue of their training, genetic counselors are well suited to address many of those challenges and to assume a variety of roles related to genetics education for health professionals. This paper provides a brief overview of the status of genetics education for non-genetics health professionals and reviews the context in which educational efforts are likely to occur.

Abstract: What does it mean to have a disability? Who comprises the “target audience” for genetic counseling services, and what are its goals? While these questions are not new to genetic counselors, the authors of Theology, Disability and the New Genetics ask them from Christian theological perspectives. Provocative, and perhaps controversial, this attempt at science–religion dialogue may be useful for health providers to learn some theological perspectives, and perhaps for Christian theologians to glimpse the world of genetics. The book is the outcome of a 2005 symposium at University of Aberdeen Centre for Spirituality, Health and Disability. It is an edited volume of individual chapters written by (mostly) theologians (one self-identifying as having a disability), ethicists, a neonatal nurse who is the mother of a child with Down syndrome, a couple of physicians, and a virologist/geneticist. Divided into four main sections, the book includes discussion of various definitions and views of disability (Part 1), an historical and descriptive account of eugenics (Part 2), a review of molecular genetics and genetic epidemiology (Part 3), and theological reflections on disability and genetics (Part 4). Despite the promise of the book’s title and structure, the practical usability of the text may be limited to Christian readers. This limitation is hinted in the book’s subtitle, “Why Science Needs the Church.” It is informative that the text is not subtitled, “Why the Church Needs Science”, or, better yet, “Why Science and the Church Need Each Other.” The latter two titles would have been more inviting of dialogue, particularly since the editors’ perspective is primarily from within theology. Thus, the book is enlightening and compelling if the reader is willing to accept faithbased beliefs such as “...the fact that human beings [are] particular objects of God’s love and salvific intentions...by virtue of our Adamic inheritance” (p. 11); or “...the transformative fact that God is the decisive player in all development with the new genetics” (p. 15). Emphasis on these assumptions may serve to weaken the theologians’ arguments for non-Christian readers. Many of the arguments and topics are not necessarily “new”, despite the implication in the title. For example, the social model of disability—acknowledging that “disability” is socially constructed and not a static characteristic of individuals—has been around since at least the 1970s (Iezzoni and Freedman 2008). The use of person-centered language (e.g., “child with Down syndrome”, rather than “Down syndrome child”) and patient-centered care are certainly not new to genetic counseling. Similarly, practitioners of medical genetics and genetic counselors daily confront questions related to eugenics, abortion, prenatal diagnosis, and the “expressivist argument” (i.e., prenatal screening for disabilities could comment adversely on the value of persons now living with those disabilities). Although “new” is not explicitly defined in the text, it does not quite seem to be an appropriate descriptor in the title, especially since so much of the text focuses on prenatal diagnosis for Down syndrome, which has been occurring for nearly four decades. In contrast, two chapters are devoted to describing the state-of-the-science. Although it is intended for a lay audience, one of the chapters gives a highly technical account of molecular genetics and epigenetics without much comment on the topic of disability. Another chapter gives a much more comprehensible account of genetics, J Genet Counsel (2008) 17:406–407 DOI 10.1007/s10897-008-9155-2

Abstract: The correct name of the eighth author should be given as Sik-To Lai, not Jak-Yiu Lai.

Abstract: Development of statistical tests to detect selection (strictly speaking, departures from the neutral equilibrium model) has been an active area of research in population genetics over the last 15 years. With the advent of dense genome sequencing of many domesticated crops, some of this machinery (which heretofore has been largely restricted to human genetics and evolutionary biology) is starting to be applied in the search for genes under recent selection in crop species. We review the population genetics of signatures of selection and formal tests of selection, with discussions as to how these apply in the search for domestication and improvement genes in crops and for adaptation genes in their wild relatives. Plant domestication has specific features, such as complex demography, selfing, and selection of alleles starting at intermediate frequencies, that compromise many of the standard tests, and hence the full power of tests for selection has yet to be realized.

Abstract: Genomic and proteomic studies have identified hundreds of proteins from mitochondria. A recent study has added a functional twist to these systematic approaches and identified novel mitochondrial modifiers and regulators.

Abstract: Sirs: Familial cortical myoclonic tremor associated with epilepsy (FCMTE, also reported as BAFME, FAME or ADCME) is an autosomal dominant inherited condition characterized by adult-onset cortical myoclonus, associated with a variable epileptic phenotype in approximately half of the patients [1]. Two loci were identified on chromosome 8q23.3-q24.11 (FAME1) and 2p11.1-q12.2 (FAME2) in a Japanese family and an Italian family, respectively [2, 3], but no gene were identified yet. We previously reported a large Spanish family (including seven non-affected individuals and ten affected individuals, five presenting also with generalized clonic–tonic seizures) in which the 8q23q24 locus was excluded [4]. A genome-wide scan using 370 microsatellite markers was performed on 11 family members (6 affected). Pairwise and multipoint logarithm of the odds (LOD) scores were calculated using Allegro1.2c considering the disease as an autosomal dominant trait with a penetrance of 90% (Fig. 1a). Further analysis including all family members excluded all regions with positive LOD scores except for one. Multipoint LOD score values >3 were obtained for all markers between D2S2114 and D2S2187, encompassing the centromeric region and for a nearby region between D2S2368 and D2S441. Haplotype reconstitution confirmed the existence of a common 40.27 Mb (33.73 cM) haplotype, segregating in all ten affected family members and interrupted by a region of at least 5 Mb (Fig. 1b). One at-risk relative (IV-6), asymptomatic at age 31, also carried the haplotype. The age at onset ranging from 30 to 60 years in the family, this patient might develop the disease later on. The region identified overlaps FAME2, refining it to a 16.65 Mb (9.42 cM) between D2S2161 and D2S2264 (Fig. 1c). FCMTE being a rare syndrome, the two regions likely correspond to the same locus, although we cannot completely exclude that they are distinct. At least 141 genes have been assigned to the common interval in databases, but none is known to encode an ion channel. We selected four genes expressed in the brain that Neurogenetics (2008) 9:69–71 DOI 10.1007/s10048-007-0107-z

Abstract: Genomewide association studies are starting to turn up increasingly reliable disease markers. Monya Baker investigates where we are now and what comes next.

Abstract: Psoriasis is one of the most common chronic inflammatory dermatosis, which is observed in 0.3–7% of the world population. Numerous twin-, familial- and population-based studies suggest the involvement of genetic factors in the disease development. The present review summarizes the present state of knowledge and analyzes of the most recent findings in the molecular genetics of psoriasis.

Abstract: Background In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN) we have shown that metabolic syndrome (MetS) risk factors were moderately and significantly associated with echocardiographic (ECHO) left ventricular (LV) phenotypes.

Abstract: An 11-day-old female child, the third in birth order of a non-consanguineous couple, was found to have a double trisomy(48, XXX+21) upon karyotyping. The proband has the typi-cal Down’s syndromephenotypeand the same was attributedto trisomy-21.The occurrence of double aneuploidy is a relativelyrare phenomenon in human (MacFaul

Abstract: A report on the Maize Genetics Conference held in Washington DC, USA, 27 February-1 March, 2008.