chapter7-somaticcellgeneticsandhumangenemapping.pptVIP

* Example: DMD（Duchenne muscular dystrophy） ① X－A translocation DMD, X-linked recessive inheritance, is very rare in female. Karyotype analysis of several affected female indicated common X-A translocation. Although these translocations involved different autosomes, their broken points on X chromosomes were commonly located on Xp21. This indicated that the broken points were inner of the gene for DMD. * ② Microdeletion in X chromosome In one well-studied example, a boy with no known family history of any genetic disease presented with 4 ordinarily distinct X-linked conditions: DMD, chronic granulomatous disease CGD , retinitis pigmentosa RP , and a rare red blood cell phenotype. Careful cytogenetic analysis revealed a small but detectable deletion in band Xp21.2. Normal X Patient B.B. DMD CGD RP * 特点: 简便、直观； 用于未知基因的定位； 自然状态下，染色体畸变来源有限，很多染色体畸变的个体都被淘汰了。 Simple, convenient and intuitionistic； For mapping the unknown genes； Most of the individuals with structural chromosomal aberrations are eliminated naturally. specialities: * Technique 5--- Gene mapping by linkage analysis Linkage analysis is a method of mapping genes that uses family studies to determine whether two genes show linkage when passed on from one generation to the next. * Linkage analysis Mapping by genetic linkage analysis differs from mapping by physical methods because physical mapping relies on having a laboratory method to localize a gene by FISH or by somatic cell hybridization. In contrast, linkage analysis is a tremendously important and powerful approach in medical genetics because it is the only method that allows mapping of genes, including disease genes, that are detectable only as phenotypic traits. * Linkage Faulty gene Loci A Loci B Dd 21 12 dd 22 34 dd 12 23 dd 12 24 Dd 22 13 Dd 22 14 Dd 22 24 Dd 22 13 dd 12 23 * i.e. BDB D9S938 was linked closely with the faulty gene Recombination between D9S123 and the faulty gene Dd dd Dd dd Dd Dd dd dd Dd 21 34