Biology Reference
In-Depth Information
such analyses can be reconstructed using information on relationships
among individuals within households as outlined by Williams-Blangero
and Blangero.
31
This standardized interview process allows efficient
collection of pedigree information, and facilitates subsequent recon-
struction of extended pedigrees crossing multiple households. The
process has been used effectively in populations with varying family
structures throughout the world,
31
and was used to gather family
information in a population endemic for Ascaris infection in eastern
Nepal.
The rest of this chapter will focus specifically on how we make infer-
ences about the potential role of host genetics in Ascaris infection and
what our current state of knowledge is regarding genetic determinants of
Ascaris burden in humans.
MEASURING THE EXTENT OF HOST GENETIC
VARIATION IN INFECTION
How do we begin to assess the importance of host genetic variation in
a phenotype as complex as Ascaris variation? Fortunately, there is a large
body of study designs and statistical genetic methods that now allow us to
largely disentangle the roles of shared environment and host genetic
factors. Most of the needed framework comes from quantitative genetics.
To start with, we will ignore the major problem of shared environment
and focus purely on host genetic factors. It is clear that human quantita-
tive genetics is primarily concerned with characterizing the range of
genetic variation in populations that, given variation in environmental
exposures and population substructure, results in an observable range of
phenotype that in our specific case is a measure of Ascaris burden. An
overriding challenge, as compared to analyses of monogenic traits, is that
multiple loci may be contributing to the phenotype, so the effect size of
any locus is likely to be relatively small. In addition, there may be multiple
types of sequence variation in play, ranging from substitution of single
nucleotides to large chromosomal rearrangements. Even if the majority of
genetic effects were confined to a single locus, this could be due either to
a single variable site or to multiple rare alleles segregating in the pop-
ulation(s) under study.
Heritability is the proportion of the total variance of a phenotype that is
attributable to the additive effects of alleles. It represents an estimate of
the relative extent of genetic variation in a given phenotype. Thus,
heritability provides us with a single measure of how important a role
genes are likely to play in the causal determination of a variable human
trait such as susceptibility to Ascaris infection or burden. In a classical
variance-components-based approach to quantitative genetic analysis,
