New approach to genetic of complex multifactorial disorder and traits

The study of the genetics of complex traits is made complicated by the fact that the traits themselves are influenced by interplay of many genes with many environmental factors. In this lecture we will talk about the concept of quantitative genetic that include additive variance and heritability.A phenotype with known or suspected genetic involvement that does not conform to classical mendelian inheritance is generally described as a complex genetic trait. In truth, all genetic traits are complex because identical phenotypes among individuals carrying identical alleles at a given locus arerare or nonexistent, due to a number of causes including incomplete penetrance, genetic heterogeneity, and most often, a genetic background consisting of multiple genes modifying the phenotype with minor effects. Generally, however, we reserve the term complex for phenotypes that are influenced bymultiple genes (polygenic) as well as environmental factors. Many of the traits important to animal agriculturefall into this class and are described quantitatively rather than qualitatively. Complex traits also include phenotypes that are discrete but are only expressed when the effects of multiple genesand/or environmental factors achieve a minimal threshold. With molecular genetic markers, such as SNPs, it is possible to test whether there are differences in the measured phenotype among the genotypes at the genetic marker. Many interesting challenge arisewhen such a test is expanded to one million markers spanning the entire chromosome, a design known as genome-wide association study. Complication due to population stratification, admixture, genotype x environment interaction, epistasis and rare allele all considered. Methods that test association by useof excess of allele sharing in sibling or other relatives, or by excess cotransmission of alleles and disease state were their own set of advantages and disadvantages. We want to explore of why some considerations of why the powerful methods nevertheless leave much of the genetic variance incomplex trait unexplained. The recent discovery of the common variation of genomes from different human populations and theavailability of technical platforms for massive and low cost genotyping of hundreds of thousands of polymorphic markers in very large number of samples has made genome wide association studies (GWAS) possible for numerous human complex multifactorial phenotypes. The latter are complextraits, which are influenced by distinct combinations of multiple genetic and nongenetic factors,contributing together to a graded phenotype. GWAS were successful in identifying low risk alleles in candidate genes or loci. More importantly, these studies disclosed unexpected molecular pathways for different common, multifactorial disorders and traits.

کلیدواژه ها:

Multifactorial disorder ، genetic marker ، genome wide association studies