1. Weiying Jiang Department of Medical Genetics Screening for genetic disease p.303

2. Screening The identification of a person from a population with a particular disorder , or who carry a gene for a particular disorder.

4. Carrier testing for autosomal and recessive and X-linked disorders Carrier ?

5. Carrier Normal in appearance An individual who is heterozygous for a recessive gene that predisposes for a hereditary disease. An individual who has a disease –caused dominant gene that is delay or irregular dominance

6. Carrier An individual who has a derive chromosome of balanced translocation, balanced inversion Normal in appearance

7. Carrier An individual that carries one gene for a particular recessive trait. A carrier does not express the trait but, when mated with another carrier, can produce offspring that do. Irregular dominance Form fruste and delay Balanced translocation carrier Balanced inversion

8. Clinic manifestation in carrier Most carriers of AR and XR are no manifestation overlapping variation seen in the general population

9. Overlapping variation seen in the general population

10. Clinic manifestation in carrier A few carriers of XR have mild clinic manifestation. Careful examination carrier of X-linked Ocular Albinism carrier of hemophilia

11. X chromosome inactivity 图 3-12 X 连锁遗传女性携带者镶嵌体的形成 F M 合子 巴氏小体 早期胚胎

12. Biochemical abnormality carriers of AR and XR are Enzymatic activity levels in carriers overlap with those in normal range Detectable biochemical abnormality in carriers of certain diseases

13. G6PD/6PGD Normal G6PD/6PGD:1-1.67 G6PD/6PGD Ratio Numbers of subjects

14. DMD DMD hemizygote Increased permeability of muscular membrane Escape of the creatine kinase (CK) into blood CK increasing

15. DMD- Heterozygote CK: µ Mol/L Numbers of the heterozygote

16. Biochemical abnormality Tay-Sachs Disease Carrier testing Select life partner Faith-based objection to termination of pregnancy

17. Linkage between a disease locus and a polymorphic maker p.305 RFLP (Restriction fragment length polymorphism) STR （ short Tandem Repeat ） SNP （ Single Nucleotide Polymorphism ）

18. X-linked recessive inheritance Mother Father A b A b a B A B A B a B a B A B A b

19. RFLP

20. STR （ short Tandem Repeat ） Stands for “CA”

21. Ⅰ Ⅱ Ⅲ 1 2 1 2 3 4 1 2 3 4 Obligate carrier DMD

22. SNP （ Single Nucleotide Polymorphism ）

23. Neonatal screening P310 AminoNova services and aminoNova analyzers

24. Phenylketonuria (PKU)

25. Classical Phenylketonuria (PKU) Phenylalanine hydroxylase phenylalanine tyrosine Phenylpyruvic Acid Phenyllactic Acid Phenylacetic Acid

26. Phenylpyruvic Acid Sweat Phenyllactic Acid Urine Phenylacetic Acid Bad smell (stink like mouse urine)

27. Phenylpyruvic Acid γ aminobutyric Phenyllactic Acid Acid Phenylacetic Acid serotonin(5-HT) CNS Mental Retardation

28. Phenylalanine Acid Phenylalanine hydroxylase tyrosine tyrosinase (-) dopa melanin skin Pigment eyes hair

30. Bacillus subtilis inhibition assay is a medical test performed on newborn infants to detect phenylketonuria. Bacillus subtilis inhibition assay ( Guthrie test)

31. A spot of blood on a filter paper disc is placed on the surface of an agar plate containing β-2-thienylalanine that inhibits the growth of bacteria.

32. However, the inhibition can be overcome by high phe. After incubating the agar plate overnight, the diameter of the growth zone around the test disc is compared to that of a control disc of blood serum to which a known quantity of phe. has been added. This permits one to estimate the amount of phe in the test disc

33. Standard concentration ： 2 ， 4 ， 6 ， 8 ， 12 ， 20mg/dl Compare with the sample 2 ， 4 ， 6 ， 8 ， 12 ， 20mg/dl

34. AminoNova services and aminoNova analyzers Mass-spectrum

35. G6PD detecting

36. Population screening p311

37. Thalassemia α -Thalsssemia β -Thalsssemia

39. Blood cell analysis : mean corpuscular volume (MCV) > or =80fl mean corpuscular Hb (MCH) > or = 25

40. Normal α -Thalsssemia β -Thalsssemia

41. Biochemical testing:

42. Sickle-cell disease

43. Β-code 6 G A G > G T G Glu.> Val. Sickle hemoglobin Polymerization distortion Reducing deformability

45. Thank you!