1. DNA Analysis electrophoresis: separation of molecules in an electric field DNA moves toward the positive electrode in an electric field due to the huge number of phosphate groups in the DNA backbone DNA fragments migrate through the gel proportional to their size small pieces quickly, large pieces slowly for agarose gels, bands are usually visualized with ethidium bromide the percentage of agarose determines what size DNA is separated well

2. DNA Analysis normal agarose gels separate tens to thousands of base pairs pulsed field gels can separate thousands to 10 6 base pair range by regularly changing the direction of the electric field net direction is always toward + end acrylamide gels separate DNA down to the level of a single base

3. Per cent of children with 1st cousin parents

4. Sex Chromosomes

5. Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Fig. 11.14b Pedigree showing the transmission of the X-linked dominant trait of faulty tooth enamel

6. Sex-linked Disorders A male only receives such sex-linked alleles from his mother. (The homologous Y chromosome is always inherited from the father.) A male therefore needs only one copy of a sex- linked recessive allele to exhibit the recessive trait. In contrast, a female must inherit two such recessive alleles—one from each parent—to exhibit the trait

7. Gene variants all follow the same inheritance pattern (some exceptions)

9. Types & Size of GCRC Studies Familiy studies (linkage, sib pair &TDT) Association studies Drug metabolizing gene studies Linkage Sib pair TDT ddA Trace A/A A/G G/ G

10. Genetic diagnosis DNAmetaboliteprotein Blood gp ABO, Rh G6PD deficiency Hb variant Apo E 1-4 bilirubin phenylalanine cholesterol homocysteine

11. Genetic diagnosis DNAmetaboliteprotein Blood gp ABO, Rh G6PD deficiency Hb variant Apo E 1-4 bilirubin phenylalanine cholesterol homocysteine haemochromatosis MTHFR cystic fibrosis familial hyper- cholesterolaemia (FH)

12. Nuclear family Extended family Specialist - clinical geneticist paediatrician, cardiologist A known diagnosis: the aim of family studies is to identify relatives with, or without, a specific variant Affected person

13. Nuclear family Extended family A genetic family history can identify risk by locating relatives with relevant disorders GP, with any patient

14. Nuclear family Extended family Specialist - clinical geneticist paediatrician, cardiologist A genetic family history can identify risk by locating relatives with relevant disorders GP, with any patient A known diagnosis: the aim of family studies is to identify relatives with, or without, a specific variant Family history: a pincer movement on families

15. Different approaches from specialist and PHC perspectives CF

16. 41 Int polyp removed 40 Ca bowel 42 CoD not noted 43 4 44 67 72 59 D Ca bowel 48 D blood clot 91 D cot death D accident 49 Ca cervix 43 57 46 43 18 15

17. 41 Int polyp removed 40 Ca bowel 42 CoD not noted 43 4 44 67 72 59 D Ca bowel 48 D blood clot 91 D cot death D accident 49 Ca cervix 43 57 46 43 18 15

18. 41 Int polyp removed 40 Ca bowel 42 CoD not noted 43 4 44 67 72 59 D Ca bowel 48 D blood clot 91 D cot death D accident 49 Ca cervix 43 57 46 43 18 15

19. 12/03/2002 50 D stroke 61 hypertension D Ca ovary 48 Manic depressive D Ca ovary D stroke 60

20. 12/03/2002 50 D stroke 61 hypertension D Ca ovary 48 Manic depressive D Ca ovary D stroke 60

21. 12/03/2002 50 D stroke 61 hypertension D Ca ovary 48 Manic depressive D Ca ovary D stroke 60

22. 12/03/2002 50 D stroke 61 hypertension D Ca ovary 48 Manic depressive D Ca ovary D stroke 60

27. 38 Thalassemia carrier 69 Arrythmia 68 64 Thalassemia carrier Hysterectomy 40 Committed suicide 25 40 endometriosis Heart attack 60 Old age 80 Old age 70 Cancer 60 Cancer 70 88 Arrythmia 85 old age 80 Committed suicide 20 Committed suicide 20

28. 38 Thalassemia carrier 69 Arrythmia 68 64 Thalassemia carrier Hysterectomy 40 Committed suicide 25 40 endometriosis Heart attack 60 Old age 80 Old age 70 Cancer 60 Cancer 70 88 Arrythmia 85 old age 80 Committed suicide 20 Committed suicide 20

29. 38 Thalassemia carrier 69 Arrythmia 68 64 Thalassemia carrier Hysterectomy 40 Committed suicide 25 40 endometriosis Heart attack 60 Old age 80 Old age 70 Cancer 60 Cancer 70 88 Arrythmia 85 old age 80 Committed suicide 20 Committed suicide 20

30. Working With Human Pedigrees

31. Predicting and Treating Genetic Disorders Other tests analyze the fluid surrounding the fetus to detect chemical imbalances that point to specific disorders.

32. Karyotyping

33. Predicting and Treating Genetic Disorders Standard tests are performed on every baby born at a hospital in the United States, whether or not the baby has any family history for a particular disease. PKU (Phenylketonuria) Test a recessive disorder in which a person cannot process the amino acid phenylalanine. If the baby tests positive for phenylketonuria, the parents can put the baby on a phenylalanine-controlled diet. Such a diet is effective in preventing the mental disability that is characteristic of the untreated disorder. The test is done after 24 hours of age. A few drops of blood are taken from your baby through a heel prick. The blood test is sent to the laboratory and the result of the test will be sent to your family doctor.