Detecting Categories of Consanguinity through X Chromosomal Runs of Homozygosity

Learning about the history of consanguinity in different populations is vital to understanding both the cultural traditions of and the susceptibility to genetic diseases with those populations. Genotype analysis of individuals sampled from population groups is one method researchers can use to infer histories of consanguinity within those population groups. Studies have indicated that the total length of long runs of homozygosity (ROH) on autosomes within individuals from a population reflects the frequency of consanguineous unions within that population. However, autosomal long ROH cannot reveal information about the frequency of different types of consanguinity within a population. Cousin-cousin unions, for example, can be divided into four possible categories: patrilateral parallel, matrilateral parallel, patrilateral cross and matrilateral cross. Each of these unions would lead to the same frequency of autosomal ROH in the offspring of the unions, but they would theoretically have a different impact on the frequency of X chromosomal long ROH in the offspring. For example, patrilateral parallel and patrilateral cross cousin marriages would not lead to an increased incidence of X chromosomal long ROH. On the other hand, matrilateral cross cousin marriages would cause an increased incidence of X chromosomal long ROH, and matrilateral parallel cousin marriages would cause the greatest increase in the incidence of X chromosomal long ROH. Therefore, comparing X chromosomal ROH to autosomal ROH of individuals sampled from populations could potentially be used to ascertain which specific types of consanguinity were favored by those populations. Our study aimed to test whether comparing X chromosomal ROH to autosomal ROH of a population is an effective technique for identifying which type of consanguinity was favored by that population. For this study, we used a dataset consisting of genotype data at 11714 X-chromosomal SNPs in 1641 individuals sampled from 98 different human population groups from Asia, Africa and Europe. After identifying and classifying the runs of homozygosity within these populations, we compared X chromosomal ROH length to autosomal ROH length for those same populations (obtained from a previous study) to obtain a coefficient for each group. We hypothesized that groups such as Jewish populations and Middle Eastern populations would have the lowest ratio of X to autosomal ROH length, as studies had described these groups as favoring patrilateral parallel cousin marriages, and that African populations, East Asian populations and Central and South Asian populations would have higher ratios, as studies had described them as favoring matrilateral cross marriages. After ranking the population groups based on these coefficients, we discovered that Middle Eastern populations and Jewish populations had lower coefficients than African populations and East Asian populations, although Central and South Asia populations also had low coefficients similar to those of Middle Eastern populations and Jewish populations. Our study thus indicates that comparing X chromosomal runs of homozygosity to those of autosomes could be used to indicate which category of consanguineous union was favored within a specific population.

Keywords:  Department of Biology
Biology
Stanford
Computational Biology
Bioinformatics
Biostatistics
Statistical Biology
Jewish
Genetics
Mathematical biology
population genetics
inbreeding
consanguinity
cousin marriage
runs of homozygosity
X chromosome
Thesis
Advisor: Rosenberg Noah
Dmitri Petrov