疾病的单基因遗传.pptVIP

疾病的单基因遗传;single-gene disorder or monogenic disorder Some disorders result when a mutation causes the product of a single gene to be altered or missing. These disorders are inherited in simple patterns similar to or identical with those described by Mendel for certain discrete characteristics in garden peas. Therefore, it’s also called Mendelian diseases. ;*;1. Pedigree and Proband;;;;;;Symbols;;*;;*; 遗传性非息肉性结直肠癌(HNPCC)的发生与DNA错配修复缺陷有关，已知至少有5种错配修复（mismatch repair，MMR）基因(MSH2、MLH1、MSH6、PMS1 和PMS2 )与其有关。目前已在HNPCC患者中发现了400多种MMR 基因的突变，其中 MSH2 基因突变约占50％，MLH1 基因突变约占39％。;通过PCR扩增和序列测定, 在先证者 gDNA 中发现了MSH2 基因7号外显子中的一种国内外尚未见报道的新突变,该突变由于4个核苷酸（CCGA）的插入导致该4个核苷酸重复 (MSH2: c.1215_1218dupCCGA)，形成移码突变，产生异常截短蛋白。所有被检测的患者均发现该突变，表型正常的成年家系成员均正常。另外，50个家系外正常对照中未发现该基因突变。我们确认该突变导致了该家系的遗传性非息肉性结直肠癌的发生。 ;*;MSH2 mutation;2. Autosomal dominant inheritance;;;;;; There are four hallmarks of autosomal dominant inheritance: (1) Except for new mutations, which are rare in nature and extremely rare on examination pedigrees, and the complexities of incomplete penetrance to be discussed later, every affected individual has an affected biological parent. There is no skipping of generations. (2) Males and females have an equally likely chance of inheriting the mutant allele and being affected. The recurrence risk of each child of an affected parent is 1/2. ;;;;DD;;;;;;;2020/11/3;2020/11/3;There are five hallmarks of autosomal recessive inheritance: (1) Males and females are equally likely to be affected. (2) On average, the recurrence risk to the unborn sibling of an affected individual is 1/4. (3) The trait is characteristically found in siblings, not parents of affected or the offspring of affected. (4) Parents of affected children may be related. The rarer the trait in the general population, the more likely a consanguineous mating is involved. (5) The trait may appear as an isolated (sporadic) event in small sibships.;;;;? 为什么近亲婚配时子女发病风险明显增高？;2020/11/3;§ 依据亲缘系数的大小，