疾病的单基因遗传.pptVIP

疾病的单基因遗传;single-genedisorderor

monogenicdisorder

Somedisordersresultwhenamutationcausestheproductofasinglegenetobealteredormissing.ThesedisordersareinheritedinsimplepatternssimilartooridenticalwiththosedescribedbyMendelforcertaindiscretecharacteristicsingardenpeas.Therefore,it’salsocalledMendeliandiseases.

;*;1.PedigreeandProband;;;;;;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（mismatchrepair，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。

;*;MSH2mutation;2.Autosomaldominantinheritance;;;;;;Therearefourhallmarksofautosomaldominantinheritance:

(1)Exceptfornewmutations,whicharerareinnatureandextremelyrareonexaminationpedigrees,andthecomplexitiesofincompletepenetrancetobediscussedlater,everyaffectedindividualhasanaffectedbiologicalparent.Thereisnoskippingofgenerations.

(2)Malesandfemaleshaveanequallylikelychanceofinheritingthemutantalleleandbeingaffected.Therecurrenceriskofeachchildofanaffectedparentis1/2.

;;;;DD;;;;;;;2020/11/3;2020/11/3;Therearefivehallmarksofautosomalrecessiveinheritance:

(1)Malesandfemalesareequallylikelytobeaffected.

(2)Onaverage,therecurrencerisktotheunbornsiblingofanaffectedindividualis1/4.

(3)Thetraitischaracteristicallyfoundinsiblings,notparentsofaffectedortheoffspringofaffected.

(4)Parentsofaffectedchildrenmayberelated.Therarerthetraitinthegeneralpopulation,themorelikelyaconsanguineousmatingisinvolved.

(5)Thetraitmayappearasanisolated(sporadic)eventinsmallsibships.;;;;?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，