dna analysis electrophoresis: separation of molecules in an electric field dna moves toward the...
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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
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B'h
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erts
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SW
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N C
entr
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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.