Genetic Variation and disorders

Question 1

What are the different kinds of chromosomal disorders?

Answer 1

• Gain or loss of a whole chromosome
• Rearrangement of whole or part of the chromosome
• Gain or loss of part of a chromosome

Question 2

What is a robertsonian translocation?

Answer 2

Translocation between 2 acrocentric chromosomes

Question 3

What is Klinefelter syndrome?

Common presentations

Answer 3

47XXY
Most common cause of primary male hypogonadism
Low testosterone, small testes, tall, wide feminine hips and gynacomastia, behavioural phenotype and low IQ

Question 4

What is Turner’s Syndrome

Common Presentations

Answer 4

45XO

Short, stature, shield chest, webbed neck, bicuspid aortic valves and coarctation of the aorta, infertility

Question 5

What are microdeletions and microduplications?

Can they be seen on conventional karyotypes?

Answer 5

Genetic material is missing or duplicated.

Cannot be seen on conventional karyotypes - must lose or gain 3-5 million base pairs to see it

Question 6

What is the risk of a child of a parent with an AD disease inheriting the disease?

Answer 6

50% chance the child has the disease

Question 7

What is the risk of a child inheriting a AR disease if both parents are carriers?

Answer 7

25% chance the child has the disease.
50% chance of being a carrier
25% no disease

Question 8

What is the pattern of inheritance of AD diseases?

Answer 8

M=F.

Usually effects each generation but may skip if incomplete penetrance

Question 9

What is the pattern of inheritance of AR diseases?

Answer 9

M=F.
Horizontal appearance of phenotype, especially among siblings.
Consanguinity increases phenotypes

Question 10

What is the pattern of inheritance of X linked diseases?

Answer 10

Affected allele is on the X chromosome =
Fathers –> all daughters are carriers
XR Mothers –> half of sons have disease and half of daughters are carriers
XD Mothers –> all sons have disease and all daughters have phenotypic disease. Usually fatal to sons
NO MALE TO MALE INHERITANCE

Question 11

X-inactivation

Answer 11

All females have X-inactivation –> lyonisation. Each cell can only use 1 copy of X chromosome therefore 1 copy is randomly inactivated . Skewed X inactivation can result in symptoms of XR diseases in females

Question 12

What are triple repeat disorders

Answer 12

Expanded repeats of triple codons resulting in disease. Allele expansion dependent on gender of transmitting parent
Huntingtons = paternal
Myotonic dystrophy = Maternal

Question 13

Anticipation?

Answer 13

The observation that a particular phenotype is increasing in severity across generations

Question 14

What are the regulators of gene expression? What is this called?

Answer 14

EPIGENETICS

Gene expression is regulated by histone modification, DNA methylation, and availability of transcription factors

Question 15

What is imprinting?

Answer 15

Differential expression of a gene according to the parent of origin. A normal process in some genes.
Diseases result when there is loss of the normal gene in the parent which is to be expressed.
Resets each generation

Question 16

What are examples of imprinting disorders?

Answer 16

15q12
Angelman syndrome Absent maternal allele expression = maternal imprinting
Prader Willi Syndrome. Absent paternal allele expression. = paternal imprinting

Question 17

What is the 2/3rd rule

Answer 17

For conditions which are AR inheritance the carrier risk of a sibling is 2/3

Question 18

How to work out the incidence of a recessive condition

Answer 18

Carrier frequency b/a

Incidence = b/(axa) x 4

Question 19

What is the Hardy Weinberg principle?

Answer 19

p2+q2+2pq=1

Question 20

What is the pattern of inheritance of imprinting disorders?

Answer 20

Maternal imprinting =

• Half of her sons children will have disease
• None of her daughters children will have disease

Paternal imprinting =

• None of his sons children will have the disease
• Half of his daughters children will have the disease

Question 21

What is the pattern of inheritance of mitochondrial diseases?

Answer 21

Only from mothers to their children
Disease affects males and females equally
Disease depends on mutation load in each daughter cell

Eg: MELAS, MERRF, NARP, Leigh syndrome

Question 22

What is linkage disequailibrium?

Answer 22

The tendency for alleles to be inherited together in a non-random fashion
Occurs when 2 genes are close in chromosomal position

Question 23

If both parents of a child with a genetic condition have negative tests is there no chance of having another child with the condition?

Answer 23

No

Parents may be gonadal mosaics