Transcript Per cent of children with 1st cousin parents

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
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
0
Great Britain
SW Peninsula
Dorset & Somerset
Chesh & Mersey
N & E Yorks & N Lincs
Kent & Medway
Essex
Hamps & IoW
Avon Glouc & Wilts
Wales
Norfk, Suffk & Cambs
Surrey & Sussex
SE London
Nthumber Tyne & Wear
Leics N'thants & Rutld
Durham & Tees Vall
Cov War Heref & Worcs
Trent
Shropsh & Staffs
N Centr London
SW London
S Yorkshire
Bedfdsh & Herts
Thames Valley
Cumbria & Lancs
NW London
Gter Manchester
NE London
B'ham & Bl Country
W Yorkshire
% of children
Per cent of children with 1st cousin
parents
7
6
5
4
Ethnic minority
1C parents
3
2
N Euro 1C
parents
1
Sex Chromosomes
Fig. 11.14b Pedigree showing the transmission of the X-linked
dominant trait of faulty
tooth enamel
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
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 sexlinked 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)
Partner who
carries a gene
variant
Not a carrier
Partner who does
not carry the
variant
Carrier of the
gene variant
Not a carrier
Carrier of the
gene variant
Gene variants all follow the
same inheritance pattern (some
exceptions)
Partner who
carries the same
gene variant
Partner who
carries a gene
variant
Not a carrier
Carrier of the
gene variant
Carrier of the
gene variant
Person
homozygous for
the gene variant
Types & Size of GCRC Studies
• Familiy studies
(linkage, sib pair
&TDT)
TDT
Linkage
Sib pair
• Association studies
• Drug metabolizing
gene studies
ddA
Trace
A/A
A/G
G/
G
Genetic diagnosis
DNA
protein
metabolite
Blood gp ABO, Rh
G6PD deficiency
Hb variant
Apo E 1-4
bilirubin
phenylalanine
cholesterol
homocysteine
Genetic diagnosis
DNA
haemochromatosis
MTHFR
cystic fibrosis
familial hypercholesterolaemia (FH)
protein
metabolite
Blood gp ABO, Rh
G6PD deficiency
Hb variant
Apo E 1-4
bilirubin
phenylalanine
cholesterol
homocysteine
Extended
family
Nuclear
family
Specialist -
Affected
person
clinical geneticist
paediatrician, cardiologist
A known diagnosis:
the aim of family studies is to
identify relatives with, or without, a
specific variant
Extended
family
Nuclear
family
GP, with any patient
A genetic family history can identify
risk by locating relatives with relevant
disorders
Family history: a pincer movement
on families
Extended
family
Nuclear
family
Specialist clinical geneticist
paediatrician, cardiologist
A known diagnosis:
the aim of family studies is to
identify relatives with, or without, a
specific variant
GP, with any patient
A genetic family history can identify
risk by locating relatives with relevant
disorders
Different approaches from specialist
and PHC perspectives
A CF
Spec ialist
B
C
Primary c are
D Ca bowel 48
59
67
D cot death D accident
D blood clot 91
72
49
57
Ca cervix 43
Ca bowel 42 CoD not noted
46
43
44
41
43
Int polyp removed 40
18
15
4
D Ca bowel 48
59
67
D cot death D accident
D blood clot 91
72
49
57
Ca cervix 43
Ca bowel 42 CoD not noted
46
43
44
41
43
Int polyp removed 40
18
15
4
D Ca bowel 48
59
67
D cot death D accident
D blood clot 91
72
49
57
Ca cervix 43
Ca bowel 42 CoD not noted
46
43
44
41
43
Int polyp removed 40
18
15
4
D stroke 60
D stroke 61
hypertension
D Ca ovary
50
D Ca ovary 48
Manic depressive
D stroke 60
D stroke 61
hypertension
D Ca ovary
50
D Ca ovary 48
Manic depressive
D stroke 60
D stroke 61
hypertension
D Ca ovary
50
D Ca ovary 48
Manic depressive
D stroke 60
D stroke 61
hypertension
D Ca ovary
50
D Ca ovary 48
Manic depressive
77
74
73
D heart attack 55
D emphysema 77 D heart attack 71
? No.
54
? No.
51
41
36
56
51
53
Epilepsy
Asthma
Asthma
Alzheimer's 50
? No.
27
25
18
Asthma 1
Asthma 1
Hay fever
Asthma/ eczema 1
Food allergies
to 11yr
77
74
73
D heart attack 55
D emphysema 77 D heart attack 71
? No.
54
? No.
51
41
36
56
51
53
Epilepsy
Asthma
Asthma
Alzheimer's 50
? No.
27
25
18
Asthma 1
Asthma 1
Hay fever
Asthma/ eczema 1
Food allergies
to 11yr
77
74
73
D heart attack 55
D emphysema 77 D heart attack 71
? No.
54
? No.
51
41
36
56
51
53
Epilepsy
Asthma
Asthma
Alzheimer's 50
? No.
27
25
18
Asthma 1
Asthma 1
Hay fever
Asthma/ eczema 1
Food allergies
to 11yr
77
74
73
D heart attack 55
D emphysema 77 D heart attack 71
? No.
54
? No.
51
41
36
56
51
53
Epilepsy
Asthma
Asthma
Alzheimer's 50
? No.
27
25
18
Asthma 1
Asthma 1
Hay fever
Asthma/ eczema 1
Food allergies
to 11yr
old age 80
old age 80 Committed Committed
suicide 20 suicide 20
Cancer 70
88
Heart attack 60 Old age 80
Arrythmia 85
69
Committed
suicide 25 Arrythmia 68
38
Thalassemia
carrier
64
Thalassemia
carrier
Hysterectomy 40
40
endometriosis
Old age 70
Cancer 60
old age 80
old age 80 Committed Committed
suicide 20 suicide 20
Cancer 70
88
Heart attack 60 Old age 80
Arrythmia 85
69
Committed
Arrythmia
68
suicide 25
38
Thalassemia
carrier
64
Thalassemia
carrier
Hysterectomy 40
40
endometriosis
Old age 70
Cancer 60
old age 80
old age 80 Committed Committed
suicide 20 suicide 20
Cancer 70
88
Heart attack 60 Old age 80
Arrythmia 85
69
Committed
Arrythmia
68
suicide 25
38
Thalassemia
carrier
64
Thalassemia
carrier
Hysterectomy 40
40
endometriosis
Old age 70
Cancer 60
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.