医学遗传学英文课件：diagnosis

1、The diagnosis of Genetic Diseasev Prenatal diagnosisv The overview of diagnosis of genetic diseaseOutlineTO MASTER:Prenatal diagnosis and its purposeNoninvasive prenatal diagnosisInvasive prenatal diagnosisLaboratory studiesWhat is prenatal diagnosis?Prenatal diagnosis (产前诊断产前诊断)determines the healt

2、h and condition of an unborn fetus. Its purpose:nTo detect abnormalities nTo provide a range of informed choicenTo provide reassurance and to reduce anxietynTo allow couples at risk of having an affected child to have a health onePrenatal diagnosis requires the collaboration of:ObstetricsUltrasonogr

3、aphyClinical genetics n(including genetic counseling)Laboratory servicesWhat are the indications for prenatal diagnosis?Advanced maternal agePrevious child with a de novo chromosome abnormalityPresence of structural chromosome abnormality in one of the parentsFamily history of a genetic disorder tha

4、t may be diagnosed or ruled out by biochemical or DNA analysisFamily history of an X-linked disorder for which there is no specific prenatal diagnosisWhat are the indications for prenatal diagnosis?Risk of a neural tube defectThe result of maternal serum screening is above the cut-off Ultrasound abn

5、ormalitiesWhat are the indications for prenatal diagnosis?Prenatal diagnosisNoninvasive testingnMaternal Serum Screening (MSS)nAnalysis of Cell-Free Fetal DNA nUltrasonographyInvasive testingnAmmiocentesisnChorionic villus sampling Laboratory studiesnCytogenetic testnBiochemical testnGene test Mater

6、nal serum screening (MSS)Measuring three blood markers:nAlphafetoprotein (AFP)甲胎蛋白甲胎蛋白 nunconjugated estriol (uE3)雌三醇雌三醇nhuman chorionic gonadotrophin (hCG) 人绒毛膜促性腺激素人绒毛膜促性腺激素Performed between 15-20+6 weeks gestational ageTriple Marker Screen The test modifies a womans risk for :Down SyndromeTrisomy

7、 18Neural Tube Defects (NTD)AFPMade by the fetal liver; function unknownNormally AFP carried into amniotic fluid by fetal urine.Passes into maternal serum by placental diffusionMaternal Serum AFPNeural Tube Defects - 4x higherDown Syndrome - 25% lowerTrisomy 18 - lowerPatternsNoninvasive Prenatal di

8、agnosis by Analysis of Cell-Free Fetal DNA After 7 weeks of gestation, cell-free fetal DNA is floating in the maternal circulationThe cell-free fetal DNA is derived from the placental trophoblastsHigh-throughput sequencing technologyWith sensitivities and specificities approaching 99% for trisomy 21

9、Prenatal diagnosis by ultrasonographyChromosomal aneuploidySingle-gene disordersMultifactorial disordersDetermination of fetal sexInvasive testingAmniocentesisn15-16 weeks gestationnMiscarriage and clubfoot (talipes equinovarus)Chorionic villus samplingn10-12 weeks gestationnFetal loss CVS can be us

10、ed for :nChromosome studynDNA tests, enzyme testsAssociated with additional 1% risk of fetal loss 2% CVS samples yield ambiguous results due to chromosomal mosaicism Technique difficultiesIf fails, amniocentesis can be performedChorionic villus samplingTests:nCytogeneticnMolecular geneticComplicatio

11、nsnMiscarriage 1%nClub feet x13Amniocentesis1. Cytogenetic2. Biochemical3. MolecularTypes of Genetic TestsTrue mosaicismnMosaicism is truly present in the fetusPseudomosaicismnAn artifact occurring in tissue culture Problems in prenatal chromosomal analysis1. Cytogenetic2. Biochemical3. MolecularTyp

12、es of Genetic Tests1. Cytogenetic2. Biochemical3. MolecularTypes of Genetic TestsDirect detect the changes on genomic DNA sequenceSingle nucleotide mutation, triplet expention, micro deletion/duplication No cell culture requiredVarious methods:nPCRnPCR-SequencingnMLPADNA test(植入前遗传诊断植入前遗传诊断)Genetic counseling for prenatal diagnosisThe risk that the fetus will be affectedThe r