Unique-event polymorphism

Abstract: The large scale spread of Bantu-speaking populations remains one of the most debated questions in African population history. In this work we studied the genetic structure of 19 Bantu-speaking groups from Mozambique and Angola using a multilocus approach based on 14 newly developed compound haplotype systems (UEPSTRs), each consisting of a rapidly evolving short tandem repeat (STR) closely linked to a unique event polymorphism (UEP). We compared the ability of UEPs, STRs and UEPSTRs to document genetic variation at the intercontinental level and among the African Bantu populations, and found that UEPSTR systems clearly provided more resolution than UEPs or STRs alone. The observed patterns of genetic variation revealed high levels of genetic homogeneity between major populations from Angola and Mozambique, with two main outliers: the Kuvale from Angola and the Chopi from Mozambique. Within Mozambique, two Kaskazi-speaking populations from the far north (Yao and Mwani) and two Nyasa-speaking groups from the Zambezi River basin (Nyungwe and Sena) could be differentiated from the remaining groups, but no further population structure was observed across the country. The close genetic relationship between most sampled Bantu populations is consistent with high degrees of interaction between peoples living in savanna areas located to the south of the rainforest. Our results highlight the role of gene flow during the Bantu expansions and show that the genetic evidence accumulated so far is becoming increasingly difficult to reconcile with widely accepted models postulating an early split between eastern and western Bantu populations.

Abstract: We develop a Markov chain Monte Carlo approach for estimating the distribution of the age of a mutation that is assumed to have arisen just once in the history of the population of interest. We assume that in addition to the presence or absence of this mutation in a sample of chromosomes, we have DNA sequence data from a region completely linked to the mutant site. We apply our method to a mitochondrial data set in which the DNA sequence data come from hypervariable region I and the mutation of interest is the 9-bp region V deletion.

Abstract: Patients with autosomal recessive multisystemic disorder ataxia-telangiectasia are homozygous or compound heterozygous for mutations in the ataxia-telangiectasia mutated (ATM) gene. Heterozygous carriers of an ATM germline mutation have an increased susceptibility for breast cancer. The subject of this study is one particular germline mutation, the ATM exon 11 splice-site mutation IVS10-6T>G, that has been identified as being associated with an increased risk for breast cancer both in the general population and in high-risk breast cancer families. We investigated the natural history of this mutation, i.e., whether it is frequently arising de novo in a population, or whether it can be traced back to a single ancient mutational event. Genotyping of a number of polymorphic markers (two extragenic and two intragenic microsatellite loci, a single nucleotide insertion/deletion polymorphism, and a dinucleotide insertion/deletion polymorphism) was performed in 18 samples from different populations carrying the IVS10-6T>G mutation (17 unrelated breast cancer patients who were heterozygous carriers of this mutation and a single A-T patient who was homozygous for the IVS10-6T>G mutation). The same markers were also genotyped among 39 unrelated healthy individuals without this mutation. Haplotype analyses revealed one common ancestor in all mutation carriers. By means of a maximum likelihood method, we estimated the age of this mutation to be approximately 2,000 generations. We provide evidence that the IVS10-6T>G mutation occurred only once during human evolution, at least 50,000 years ago. Our results predict that this mutation could be widely distributed across Europe and, probably, the Middle East and Western Asia.

Abstract: Linguistic evidence suggests that West Asia and Central Asia have been the two major geographical sources of genes in the contemporary Indian gene pool. To test the nature and extent of similarities in the gene pools of these regions we have collected DNA samples from four ethnic populations of northern India, and have screened these samples for a set of 18 Y-chromosome polymorphic markers (12 unique event polymorphisms and six short tandem repeats). These data from Indian populations have been analysed in conjunction with published data from several West Asian and Central Asian populations. Our analyses have revealed traces of population movement from Central Asia and West Asia into India. Two haplogroups, HG-3 and HG-9, which are known to have arisen in the Central Asian region, are found in reasonably high frequencies (41.7% and 14.3% respectively) in the study populations. The ages estimated for these two haplogroups are less in the Indian populations than those estimated from data on Middle Eastern populations. A neighbour-joining tree based on Y-haplogroup frequencies shows that the North Indians are genetically placed between the West Asian and Central Asian populations. This is consistent with gene flow from West Asia and Central Asia into India.