單基因遺傳病的研究策略ppt課件

1、數(shù)據(jù)庫(kù)數(shù)據(jù)庫(kù) 中的中的OMIMOnline Mendelian Inheritance in Man 數(shù)據(jù)庫(kù)中整合數(shù)據(jù)庫(kù)中整合了目前已定位的單基因病的信息了目前已定位的單基因病的信息 確定本人所研討家系的能夠知候選基因或已定位確定本人所研討家系的能夠知候選基因或已定位的染色體候選區(qū)域的染色體候選區(qū)域從數(shù)據(jù)庫(kù)中查閱目的基因從數(shù)據(jù)庫(kù)中查閱目的基因的相關(guān)信息的相關(guān)信息突變分析結(jié)果的判別突變分析結(jié)果的判別連鎖連鎖 重組重組基因克?。捍_定致病基因基因克?。捍_定致病基因Gene map locusGRCh37.p5 Primary Assembly (STS)P h y s

2、 i c a l distance (Mb)Genetic Distance(cM)Genetic Map(Marshfield)(cM)Xp22.32-p22.25,761,897-12,538,7316.785.0715.42-20.49 Xp21.2-p21.131,289,217-32,011,2660.720.5733.05-33.62 Xq24-q27.2117,088,056-140,038,59422.9515.2670.80-86.06Gene map locusGRCh37.p5 Primary Assembly (STS)Physical distance(Mb)G e

3、n e t i c Distance(cM)Marshfield(cM)Xp22.32-p22.25,761,897-9,946,6564.182.1015.42-17.52 Xq24-q27.2117,088,056-140,038,59422.9515.2670.80-86.06 Genotype和和Phenotype相關(guān)性研討相關(guān)性研討單基因遺傳病發(fā)病機(jī)制的單基因遺傳病發(fā)病機(jī)制的研討研討 隱性突變往往導(dǎo)致失去功能loss of function 顯性突變可導(dǎo)致獲得功能gain of function和失去功能 失去功能：?jiǎn)伪秳┝咳狈alpoinsufficency 獲得功能：顯性負(fù)效應(yīng)

4、dominant negtive SSCP analysis DNA sequencing PAX6 基因及其基因及其 cDNAPAX6的功能的功能Hill et al. Nature 354, 1991;St-Onge et al. Nature 387, 2019; Sander et al. Genes Dev 11,2019Mansouri et al. TEM 10, 2019Dohrmann et al. Mech Dev 92, 2000 PAX6 在成體胰腺中的功能在成體胰腺中的功能假假 說(shuō)說(shuō) PAX6 mutation?abnormal glucose homeostasisProinsulin insulinin Pancreas POMC ACTHalpha-MSHin Hypothalamus Marcinkiewicz et al. Proc Natl Acad Sci 90, 1993 Naggert et al. Nature Genetics