DNA Analysiselectrophoresis: separation of molecules in an electric field

DNA moves toward the positive electrode in an electric field due to thehuge number of phosphate groups in the DNA backbone

DNA fragments migrate through the gel proportional to their sizesmall 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

DNA Analysis

normal agarose gels separate tens to thousands of base pairs

pulsed field gels can separate thousands to 106 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

Per cent of children with 1st cousin parents

0

1

2

3

4

5

6

7

W Y

orks

hire

B'h

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Bl C

ount

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hire

SW

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N C

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Lon

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taffs

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Wea

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Ethnic minority1C parents

N Euro 1Cparents

Sex Chromosomes

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

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

Gene variants all follow the same inheritance pattern (some

exceptions)P a r tn e r w h o

c a rr ie s a g e n e v a r ia n t

P a r tn e r w h o d o es n o t c a rry th e

v a r ia n t

N o t a c a r r ie rC a rr ie r o f th e g e n e v a ria n t

C a rr ie r o f th e g e n e v a ria n t

N o t a c a r r ie r

Gene variants all follow the same inheritance pattern (some

exceptions)P a r tn e r w h o

c a rr ie s a g e n e v a r ia n t

P a r tn e r w h o c a rr ie s th e s a m e

g e n e v a ria n t

C a rr ie r o f th e g e n e v a ria n t

C a rr ie r o f th e g e n e v a ria n t

P e r so n h o m o z y g o u s fo r th e g e n e v a ria n t

N o t a c a r r ie r

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/GG/G

Genetic diagnosis

DNA metaboliteprotein

Blood gp ABO, RhG6PD deficiencyHb variantApo E 1-4

bilirubinphenylalaninecholesterolhomocysteine

Genetic diagnosis

DNA metaboliteprotein

Blood gp ABO, RhG6PD deficiencyHb variantApo E 1-4

bilirubinphenylalaninecholesterolhomocysteine

haemochromatosisMTHFRcystic fibrosisfamilial hyper-cholesterolaemia (FH)

Nuclear family

Extendedfamily

Specialist - clinical geneticistpaediatrician, cardiologist

A known diagnosis:the aim of family studies is to identify relatives with, or without, a specific variant

Affected person

Nuclear family

Extendedfamily

A genetic family history can identify risk by locating relatives with relevant disorders

GP, with any patient

Nuclear family

Extendedfamily

Specialist - clinical geneticistpaediatrician, 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

Different approaches from specialist and PHC perspectives

Sp e c ia list Prim a ry c a re

A CBCF

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

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

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

50

D stroke 61hypertension

D Ca ovary 48Manic depressive

D Ca ovary

D stroke 60

50

D stroke 61hypertension

D Ca ovary 48Manic depressive

D Ca ovary

D stroke 60

50

D stroke 61hypertension

D Ca ovary 48Manic depressive

D Ca ovary

D stroke 60

50

D stroke 61hypertension

D Ca ovary 48Manic depressive

D Ca ovary

D stroke 60

12/03/2002

25

Asthma 1Hay fever

56

51

Epilepsy Asthma

27

Asthma 1

18

Asthma/eczema 1Food allergies

to 11yr

54

51

41

36

D heart attack 55

77

74

53

Asthma Alzheimer's 50

? No.? No.

D emphysema 77

D heart attack 71

73

? No.

12/03/2002

25

Asthma 1Hay fever

56

51

Epilepsy Asthma

27

Asthma 1

18

Asthma/eczema 1Food allergies

to 11yr

54

51

41

36

D heart attack 55

77

74

53

Asthma Alzheimer's 50

? No.? No.

D emphysema 77

D heart attack 71

73

? No.

12/03/2002

25

Asthma 1Hay fever

56

51

Epilepsy Asthma

27

Asthma 1

18

Asthma/eczema 1Food allergies

to 11yr

54

51

41

36

D heart attack 55

77

74

53

Asthma Alzheimer's 50

? No.? No.

D emphysema 77

D heart attack 71

73

? No.

12/03/2002

25

Asthma 1Hay fever

56

51

Epilepsy Asthma

27

Asthma 1

18

Asthma/eczema 1Food allergies

to 11yr

54

51

41

36

D heart attack 55

77

74

53

Asthma Alzheimer's 50

? No.? No.

D emphysema 77

D heart attack 71

73

? No.

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

old age 80

Committed suicide 20

Committed suicide 20

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

old age 80

Committed suicide 20

Committed suicide 20

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

old age 80

Committed suicide 20

Committed suicide 20

Working With Human Pedigrees

Predicting and Treating Genetic Disorders

• Other tests analyze the fluid surrounding the fetus to detect chemical imbalances that point to specific disorders.

Karyotyping

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.