內(nèi)容文稿案例12screening

1、Weiying Jiang Department of Medical GeneticsScreening for genetic disease p.313ScreeningThe identification of a person from a population with a particular disorder , or who carry a gene for a particular disorder.ScreeningTargeted, or family screening: -carrier screening -presymptomatic testingPopula

2、tion screeningCarrier testing for autosomal dominant and recessive, X-linked disorders and chromosome disorders Carrier ?CarrierNormal in appearanceAn individual who is heterozygote for a recessive gene that predisposes for a hereditary disease. CarrierNormal in appearanceAn individual who has a dom

3、inant gene that is irregular （不規(guī)則顯性） or delay dominance （延遲顯性）CarrierAn individual who has a derive chromosome of balanced aberration (平衡畸變）Normal in appearance14/21Clinical Manifestations in Carriers Most carriers of AR and XR areno manifestationThey overlap with the variation seen in the general p

4、opulation.Clinic manifestation in heterozygoteA few heterozygote of XR have mild clinic manifestation.Careful examination Hemophilia AFemale carriers of hemophilia who have a tendency to bruise easilyThis is not a reliable sign of carrier statusBiochemical features in heterozygoteHeterozygote of AR

5、and XR areA few of them with detectable biochemical abnormalityMost of them without detectable biochemical abnormalityExample: DMD (p.314)DMD hemizygote (半合子）Increased permeability of muscular membraneEscape of the creatine kinase (CK) into plasmaCK increasing DMD heterozygote Lyons hypothesisIn 196

6、1 Dr Mary Lyon proposed that this heteropyknotic X chromosome was inactivated, citing as evidence her observations on the mosaic pattern of skin coloration seen in mice known to be heterozygous for X-linked genes that influence coat color.The process of X chromosome Inactivity occurs early in develo

7、pment at around 15 to 16 days gestation, when the embryo consists of approximately 5000 cells. Normally either of the two X chromosomes can be inactivated in any particular cell randomly. Thereafter the same X chromosome is inactivated in all daughter cells X chromosome inactivity is random圖 3-12 X連

8、鎖遺傳女性攜帶者鑲嵌體的形成FM 合子巴氏小體早期胚胎p103圖 3-12 X連鎖遺傳女性攜帶者鑲嵌體的形成FM 合子巴氏小體早期胚胎clonally inherited If heterozygous females for HA, there were two cell populations of erythrocytes in such heterozygotes: F8 deficient cells normal cells Whether the female has clinic manifestation depending on the proportion of F8 d

9、eficient cells and normal cells Ratio of F8 deficient cells and normal cellsphenotype圖 3-12 X連鎖遺傳女性攜帶者鑲嵌體的形成FM 合子巴氏小體早期胚胎mosaicG6PD detectingG6PD/6PGDNormal G6PD/6PGD:1-1.67 G6PD/6PGD RatioNumbers of subjectsBiochemical abnormalityTay-Sachs Disease (家族性黑蒙性癡呆） Hexosaminidase A deficiency in Jewish 氨基

10、己糖苷酶Biochemical testingSelect life partnerFaith-based objection to termination of pregnancyNeonatal screening P318Phenylketonuria (PKU)Galactosemia Congenital hypothyroid G6PD deficiencyHearing lossPhenylketonuria (PKU)Phenylalanine hydroxylaseLow-phenylalanine dietTandem mass spectrometryMS/MSioniz

11、ationLow-phenylalanine dietPresymptomatic Diagnosis ofAutosomal Dominant Disorders Autosomal dominant polycystic kidney diseaseextremely variabledelayed age of onsetPKD (Polycystic kidney disease)Kidney failurePresymptomatic Diagnosis of PKDControl blood pressureTreating chronic nephritic proteinuri

12、a. Preventing from Kidney failurePopulation screening p318Thalassemia-Thalsssemia-ThalsssemiaBlood cell analysis :mean corpuscular volume (MCV) or =80flmean corpuscular Hb (MCH) or = 25pgBiochemical testing: Hb ElectrophoresisDetecting -Thalsssemia by Gap-PCRStrip 1: normal embryo. Strip 2: codon 41-42/N. Strip 3: IVS II 654/N. Strip 4: codon 41-42/ IVS-II-654. Sickle cell anemia： 1.35 kb1.15 kb0.2 kb_+ AA AS SSElectrophoresisG6PD detectingG6PD/6PGDNormal G6