医学遗传学Complex Dis.pptVIP

Genetics of Complex Traits and Diseases ZHANG Xian-Ning, PhD zhangxianning@ Tel Office: C303, Teaching Building 2014/10 Any disease is the result of the combined action of genes and environment Classification of genetic disorders: Chromosome disorders: Single-gene disorders: Complex (multifactorial, polygenic) disorders: Somatic cell genetic disorders: Mitochondrial genetic disorders: ABO blood group depends (with rare exceptions) on the genotype at just one locus, the ABO locus at chromosome 9q34. Rhesus hemolytic disease of the newborn depends on the genotypes of mother and baby at the RHD locus at chromosome 1p36, but also on mother and babys being ABO compatible. Hirschsprung disease depends on the interaction of several genetic loci. Adult stature is determined by the cumulative small effects of many loci. Environmental factors are also important in the etiology of Rhesus hemolytic disease, Hirschsprung disease, and adult height. Genetic Susceptibility An inherited predisposition to a disease or disorder which is not due to a single-gene cause and is usually the result of a complex interaction of the effects of multiple different genes, i.e. polygenic inheritance. Why study the genetics of common diseases? Understanding the underlying genetics will lead to understanding the causes, which may lead to better and more specific therapies Identification of the responsible genes helps to identify those who are at risk in families and in the population, allowing individualized health assessment and targeted prevention How to Determine the Genetic Components of Complex Diseases? Family, twin and adoption studies Segregation analysis Linkage analysis Association studies and linkage disequilibrium Identification of DNA sequence variants conferring susceptibility Trait: Any detectable phenotypic property or character. Qualitative trait: A genetic disease trait that either present or absent. The pa