Population stratification and genetic association studies in South Asia

Population stratification and its influence on genetic association studies is a controversial topic. Although it has been suggested that stratification is unlikely to bias the results of association studies conducted in developed countries, convincing contrary empirical evidence has been published. However, it is in populations where historical ethnic, religious and language barriers exist that community subdivisions will predictably exert greatest genetic effect, and influence the organization of association studies. In many of the populations of the Indian sub-continent, these basic population divisions are compounded by a strict tradition of intracommunity marriage and by marriage between close biological relatives. Data on the very significant levels of genetic diversity that characterize the populations of India and Pakistan, with some 50,000-60,000 caste and non-caste communities in India, and average first cousin marriage rates of 40%-50% in Pakistan, are presented and discussed. Under these circumstances, failure to explicitly control for caste/biraderi membership and the presence of consanguinity could seriously jeopardize, and may totally invalidate, the results of association/case control studies and clinical trials

Infant and child mortality in rural Egypt: A comment

In their interesting analysis of infant and child mortality in rural Egypt, derived from data collected as part of the World Fertility Survey in 1980, Castleline, Cooksey & Ismail (1992) specifically noted the significant differentials in neonatal and early infant mortality which existed between Lower and Upper Egypt. The differentials could not be explained in terms of socioeconomic variables, the household sanitary environment, maternal risk factors or medical institutions and personnel. Conversely, it was suggested that they could be attributed to fundamental though unidentified cultural differences between two regions

The triple challenges associated with age-related comorbidities in Down syndrome

Background Major increases in the survival of people with Down syndrome during the last two generations have resulted in extended periods of adulthood requiring specialist care, which in turn necessitates greater understanding of the nature, timing and impact of comorbidities associated with the disorder. Method The prevalence of five comorbidities reported as common in adults with Down syndrome, visual impairment, hearing impairment, epilepsy, thyroid disorders and dementia was assessed by decade of life. Results From early adulthood, people with Down syndrome are at enhanced risk of developing new comorbidities and they may present with multiple conditions. Three specific challenges are identified and discussed: are comorbidities detected in a timely manner, is the clinical progress of the disorder adequately understood, and who is responsible for the provision of care? Conclusions Further detailed investigations into the development and treatment of comorbidities across the lifespan are needed for a successful longitudinal approach to healthcare in people with Down syndrome. Implementation of this approach will better inform healthcare providers to ensure continuity of care with advancing age

Consanguinity, genetics and definitions of kinship in the UK Pakistani Population

YesConsanguineous marriage is a controversial topic in many Western societies, with attention mainly focused on the health of immigrant communities from Asia and Africa. In the UK consanguinity is especially prevalent in the Pakistani community which now numbers over 1.1 million. Less attention has been paid to the influence of hereditary population stratification within Pakistani communities. In particular, biraderi (literally brotherhood) membership which denotes male lineages that largely govern marriage partner choice and hence the transmission of disease genes. The various roles played by biraderi and their relationship to other socio-occupational and kinship terms, such as caste, quom and zat, are often overlooked in health-based studies. The interchangeable use of these different kinship terms without rigorous definition can create identity uncertainty and hinders inter-study comparisons. Where feasible, standardization of terminology would be both desirable and beneficial, with biraderi the preferred default term to identify specific social and genetic relationships within the Pakistani diaspora

A genome-based study of the Muslim Hui community and the Han population of Liaoning province, PR China

To investigate the proposed historical origins of the Hui, a Chinese Muslim minority resident in Liaoning Province, PR China, DNA samples obtained from 53 individuals were analyzed at ten autosomal and six Y-chromosome microsatellite loci. As reference sources, equivalent samples were investigated from the coresident Han majority population. Both the Hui and the Han exhibited appreciable genetic heterogeneity in terms of the size, number, and size range of alleles, suggestive of population substructure resulting from their particular cultural and historical backgrounds. The contrast in the patterns of autosomal and Y-chromosome diversity of the two communities was obvious. Analysis of molecular variance showed that only 4.6% of total autosomal molecular variance was due to differences between the Hui and Han. The comparable value for Y-chromosome haplotype distributions of 14.0% indicated that the Hui and Han of Liaoning have separate paternal genetic histories

The impact of consanguinity on the Indian population

Numerous studies have been conducted by Indian anthropologists into the prevalence of both consanguineous and affinal marriage.1-3 and the topic of consanguinity continues to attract great attention among geneticists and social scientists. The strengthening of family relationships is of primary importance in the preference for close kin unions, with economic benefits an additional consideration. Consanguinity does not appear to adversely affect human fertility. However, both postnatal morbidity and mortality are increased, with greatest effect so far observed in the early years of life. With declining mortality and morbidity due to infectious disease, recessive genetic disorders will progressively gain greater prominence in the overall spectrum of ill-health. This change will be especially obvious in communities which practise consanguineous marriage, and in small highly endogamous communities where random drift occurs

Genetics and global healthcare

During the course of the last decade there has been extensive discussion on the role of genetics and genomics in global healthcare, with major diagnostic advances regularly announced, such as exome sequencing to identify and classify de novo, autosomal and X-linked mutations in people with severe intellectual disability, and whole-genome sequencing for prenatal diagnosis of chromosomal anomalies, in the differential diagnosis of acute neonatal disorders, and in devising improved treatment protocols. There are, however, a number of basic issues that need to be addressed if advances of this nature are to be more widely translated in terms of healthcare

Genomics and the changing profile of human disease

Within the last decade, much has been written on the impending impact of the Human Genome Project on human health. A typical perspective was offered in 1995 as part of the submission of the Royal College of Physicians to the Science and Technology Committee of the U.K. House of Commons. In describing the future contribution of genetics to medical practice it was stated that, ‘The process has scarcely begun and may not have a major clinical impact for many years; however it represents the change from empirical to rational management of disease and hence its significance can hardly be exaggerated’. Clearly, any body of knowledge that could effect such a change would be of global importance, and if this and similar predictions prove to be correct, they would match in significance the revolution in medical practice provoked by the anatomical discoveries of the Renaissance period. The Human Genome Project was initiated in 1991, and by 2001, the first consensus sequence of the human genome was simultaneously published by publicly supported researchers (International Human Genome Sequencing Consortium 2001) and the privately financed Celera Genomics (Venter et al. 2001). Access to the growing database on genome structure and function made available through the Human Genome Project has greatly assisted medical researchers, and as a result, by March 2003 over 14,000 single gene disorders affecting both the human nuclear and mitochondrial genomes had been identified (OMIM 2003). Of itself, the recognition of specific and often very rare mutations is unlikely to change medical practice or to impinge on the everyday lives of the vast majority of the world’s population. Data on the contribution of predisposing genes to common diseases is still rudimentary, and there is limited information on non-biological factors that influence the genetic structure of human populations and thereby govern the distribution and transmission of disease mutations. An appreciation of the importance of these topics has, however, gradually been emerging, accompanied by the establishment of two new academic disciplines, Community Genetics and Public Health Genetics. The aim of this article is to briefly review the potential influence and effects of these changes on the future profile of genetic disease in industrialized and developing countries

Time to Get Real: Investigating Potential Beneficial Genetic Aspects of Consanguinity

The extensive and well-documented application of close genetic crosses in animal and plant breeding has amply demonstrated that, from a biological perspective, inbreeding is not necessarily detrimental, although a substantial price may have to be paid with respect to reduced viability and vigor in some progeny. However, in terms of specific phenotypic characteristics, and as long as the intensity of inbreeding does not become excessive, the benefits of selecting for specific recessive traits can outweigh the disadvantages