Genetic Basis Of Complex Traits Research Articles

Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains.

The "large" (LG/J) and "small" (SM/J) inbred mouse strains differ for a wide variety of traits related to body size and obesity. Ninety-three LG/J and SM/J mice were divided into two treatment categories and fed a moderately high-fat diet (21% kcal fat) or a low-fat diet (12% kcal fat) from weaning to necropsy. Strain differences in obesity-related traits and differential response to dietary fat increases were analyzed using ANOVA. LG/J animals grow faster from 3 to 10 wk, have longer tails, and have heavier body weight, liver weight, and fat pad weight than SM/J animals. SM/J animals grow faster after 10 wk of age and have higher fasting glucose levels than LG/J animals. SM/J mice were more responsive to increased dietary fat than LG/J mice for growth after 10 wk, necropsy weight, liver weight, fat pad weights, and fasting glucose levels (in males). The growth from 3 to 10 wk had a much greater response in the LG/J strain, whereas tail length had no response. This pattern of dietary response is similar to that expected under the "thrifty" phenotype hypothesis. Genes affecting strain differences and the differential response of the strains to dietary fat can be successfully mapped in the intercross of the LG/J and SM/J strains. This intercross provides an excellent multigenic model for the genetic basis of complex traits and diseases related to body size and obesity.

Genetics of complex disease: approaches, problems, and solutions.

Complex or multifactorial diseases are defined as diseases that are ultimately determined by a number of genetic and environmental factors. Although there are many technologies and strategies that can be used to detect genetic factors influencing complex diseases, these technologies and strategies have inherent limitations. In fact, the very name "complex disease" suggests that the results from relevant studies will not be simple to decipher. Ultimately, both the detection and precise characterization of a factor's contribution to a complex disease are difficult undertakings, because the effect of any one factor may be obscured or confounded by other factors. However, the genetic dissection of complex diseases can be greatly facilitated by paying heed to two very basic distinctions. The first distinction is between complexity at the level of individuals and complexity at the level of populations. The second distinction is between the two sequentially pursued components of gene discovery paradigms: gene identification and gene effect characterization. Although genetic epidemiology, as a research field, is oriented to both components of gene discovery for complex diseases, it is suited to gene effect characterization at the population level more than anything else. This paper reviews the origins of the genetic basis of complex traits, as well as the problems plaguing genetic epidemiologic analysis strategies, with the hope of showing how greater attention to these distinctions, as well as a greater integration of relevant knowledge, can alleviate confusion and shape future investigations. In addition, a new discipline, "phenomics" or "phenometrics," could be initiated that would complement genomic research as presently performed.

Genetic and molecular dissection of quantitative traits in rice.

Recent progress in the generation of a molecular genetic map and markers for rice has made possible a new phase of mapping individual genes associated with complex traits. This type of analysis is often referred to as quantitative trait locus (QTL) analysis. Increasing numbers of QTL analyses are providing enormous amounts of information about QTLs, such as the numbers of loci involved, their chromosomal locations and gene effects. Clarification of genetic bases of complex traits has a big impact not only on fundamental research on rice plant development, but it also has practical benefits for rice breeding. In this review, we summarize recent progress of QTL analysis of several complex traits in rice. A strategy for positional cloning of genes at QTLs is also discussed.

Comparative maps: the mammalian jigsaw puzzle

Chromosomal rearrangements such as inversions and translocations have played an important role in defining genome organization in existing mammals. The number of rearrangements that have occurred since divergence from the ‘primordial’ mammal has been modest and the distribution of these rearrangements among chromosomes seems to be random. As a result, each mammalian species has a unique arrangement of conserved and disrupted chromosomal segments as compared to other mammalian species. Genes are excellent markers for these chromosomal segments because homologies can be detected in highly divergent species. By comparing the chromosomal location of homologous genes in different species, maps of conserved chromosomal segments can be obtained. These comparative maps can be used to predict gene locations in other species, identify candidate disease genes, characterize the genetic basis for complex traits, and find modulators of disease susceptibility. Equally important is the use of comparative maps for addressing questions about genome organization and evolution.