Evidence for Extensive Transmission Distortion in the Human Genome

Abstract

It is a basic principle of genetics that each chromosome is transmitted from parent to offspring with a probability that is given by Mendel's laws. However, several known biological processes lead to skewed transmission probabilities among surviving offspring and, therefore, to excess genetic sharing among relatives. Examples include in utero selection against deleterious mutations, meiotic drive, and maternal-fetal incompatibility. Although these processes affect our basic understanding of inheritance, little is known about their overall impact in humans or other mammals. In this study, we examined genome screen data from 148 nuclear families, collected without reference to phenotype, to look for departures from Mendelian transmission proportions. Using single-point and multipoint linkage analysis, we detected a modest but significant genomewide shift towards excess genetic sharing among siblings (average sharing of 50.43% for the autosomes; P=.009). Our calculations indicate that many loci with skewed transmission are required to produce a genomewide shift of this magnitude. Since transmission distortion loci are subject to strong selection, this raises interesting questions about the evolutionary forces that keep them polymorphic. Finally, our results also have implications for mapping disease genes and for the genetics of fertility.