Journal Article

Relatedness in the post-genomic era: is it still useful?

Speed, Doug, Balding, David J.

2015

Overview

Key Points Relatedness is a fundamental concept in everyday life and in quantitative genetics. It has a central role in efforts to understand genetic mechanisms and in predicting phenotypes, as well as in population, evolutionary and forensic genetics. Traditionally, the relatedness of two individuals was measured in terms of the fraction of genome they share IBD (identity-by-descent), which is defined as inheritance from a recent common ancestor, but there are many approaches to interpreting 'recent'. A better viewpoint is given by coalescent theory: the time since the most recent common ancestor for two individuals varies along the genome and can take an essentially continuous range of possible values. There are now many different ways to measure the genetic similarity between pairs of individuals using genome-wide single-nucleotide polymorphism (SNP) data. The binary IBD versus non-IBD distinction provides a simple approximation but gives an inadequate representation of reality compared with the precision offered by the extensive data sets available nowadays. We argue that, for many applications, traditional concepts of relatedness are no longer required; instead, models and analyses can be based directly on genome similarity. There is no one best measure of genome similarity, but different measures can be evaluated on their performance in specific applications. Relatedness has traditionally been defined using pedigree-based measures, but these have serious deficiencies. With genome-wide data, SNP-based measures can now be used to directly measure genome similarity, a more useful concept than relatedness. This Review outlines ways to evaluate measures of genome similarity. Relatedness is a fundamental concept in genetics but is surprisingly hard to define in a rigorous yet useful way. Traditional relatedness coefficients specify expected genome sharing between individuals in pedigrees, but actual genome sharing can differ considerably from these expected values, which in any case vary according to the pedigree that happens to be available. Nowadays, we can measure genome sharing directly from genome-wide single-nucleotide polymorphism (SNP) data; however, there are many such measures in current use, and we lack good criteria for choosing among them. Here, we review SNP-based measures of relatedness and criteria for comparing them. We discuss how useful pedigree-based concepts remain today and highlight opportunities for further advances in quantitative genetics, with a focus on heritability estimation and phenotype prediction.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/2217 / 631/208 / Agriculture / Animal Genetics and Genomics / Biomedicine / Cancer Research / Computer Simulation / Forecasts and trends / Gene Function / Genetic research / Genetic screening / Genetic Variation / Genetics, Population - methods / Human Genetics / Humans / Identification and classification / Models, Genetic / Pedigree / Phenotype / Polymorphism, Single Nucleotide - genetics / Properties / Quantitative genetics / review-article / Single nucleotide polymorphisms