Genetic Disorders

Question 1

Sickle Cell Disease

Answer 1

• autosomal recessive
• chromosome 11, single gene substitution
• 1/2500 affected

Question 2

Cystic fibrosis

Answer 2

• autosomal recessive
• chromosome 7, single gene mutation - deletion of 3 bp
• 1/25 carriers, 1/2500 affected

Question 3

Achondroplasia

Answer 3

• autosomal dominant

- mutation in the FGFR 3 gene

Question 4

dont ever forget

Answer 4

population risk

the chances of someone not being affected at all is impossible, because there is always population risk

Question 5

huntington’s disease

Answer 5

• autosomal dominant
• late onset
• chromosome 4, repetition of 3 nucleotides in the HTT gene

Question 6

Duchenne muscular dystrophy (DMD)

Answer 6

• sex linked inheritance in men

- mutation of dystrophin protein that holds muscle together

Question 7

haemophilia

Answer 7

• sex linked in men

Question 8

which skips generations?

Answer 8

• sex linked (because daughters will only be carriers unless the father is affected and the mother is also a carrier)
• mitochondrial inheritance skips generations - can only be passed on by women, even if men were affected they cannot pass it on.
• autosomal dominant never skips generations

Question 9

Leber Hereditary Optic Neuropathy (LHON)

Answer 9

• mitochondrial inheritance

- sudden loss of vision after 20-30 yrs

Question 10

mitochondrial encephalopathy, lactic androsis, stroke (MELAS)

Answer 10

• mitochondrial inheritance

- dementia and vision loss

Question 11

uniparental diploidity

Answer 11

• is a nonmendelian complex inheritance
• gynogenote: 2 maternal sets of 46 chromosomes - tumor in uterus containing hair teeth limbs but no placenta
• androgenote: 2 paternal sets of all 46 chromosomes - molar pregnancy of bubbly placenta with no sign of embryo

Question 12

uniparental disomy

Answer 12

• nonmendelian complex inheritance
• angelman syndrome (AS)
• Prader willi syndrome (PWS)

Question 13

angelman syndrome

Answer 13

• chromsome 15
• maternal chromosome has paternal imprint
• 2 paternal copies

cases:

1. deletion of maternal copy (70%)
2. Uniparental disomy of paternal copy (1-2%)
3. imprinting of maternal by paternal copy - methylation of the maternal copy (2-4%)
4. point mutation of the UBE3A gene in the maternal copy (10%)

Question 14

Prader willi syndrome

Answer 14

• chromosome 15, same region as AS
• 2 maternal copies

causes:
1. deletion of paternal copy (70%)
2. UPD of maternal copies (25-30%)
3. imprinting - methylation of paternal copies (1-3%)
(no known point mutation)

Question 15

Down syndrome

Answer 15

• trisomy 21
• incidence 1/650-700
• life expectancy 50-60 yrs

causes:
1. nondysjunction
2. unbalanced Robersonian translocation
3. mosaicism - issue with fetal development and not the gametes

Question 16

Patau’s syndrome

Answer 16

• trisomy 13
• incidence 1/5000
• 5% die within the first month

causes:
1. nondysjunction
2. unbalanced Rbt translocation

Question 17

Edward’s syndrome

Answer 17

• chromosome 18
• incidence 1/3000
• most die within the first month

causes:
1. nondysjuction

Question 18

Klinefelter’s syndrome

Answer 18

• 47, XXY (extra X chromosome)
• incidence 1/1000
• only in men
• long limbs, infertile, mild learning difficulties, breast tissue

Question 19

Turner’s syndrome

Answer 19

• 45, X (1 less X chromosome)
• incidence 1/5000-10,000
• most die before birth
• webbed neck, short, infertile, widely spaced nipples normal IQ and lifespan.

Question 20

paracentric vs pericentrin inversion

Answer 20

paracentric is in the arms
pericentric includes the centromere

both are balanced.

Question 21

reciprocal vs Rbt translocation

Answer 21

reciprocal is translocation btw 2 normal chromosomes
Rbt is fusion of the long arms and loss of the short arms of 2 acrocentric chromosomes.

reciprocal can be balanced or unbalanced
Rbt is unbalanced.

Question 22

types of coding mutation

Answer 22

silent
missense
nonsense - missense that leads to a stop codon
frameshift

Question 23

locus specific registers for genetic diseases

Answer 23

Clinvar - genomic variation and relationship to health
Cosmic - somatic variants in cancer
Decipher - development delay 
BRCA - breast cancer (global exchange)
LOVD - leiden open variation database
DMuDB - diagnostic mutation diseases

Question 24

alamut in silico analysis tool

Answer 24

tool used to determine the location of missense location as well as its significance.

Question 25

Hardy-Weinberg equation

Answer 25

the relative frequency of population with 2 alleles p and q (p is dominant and q is recessive) should be 1:1 under the conditions that:

1. large population
2. random mating
3. no selection forces
4. no mutation and migration

Question 26

uses of HWE

Answer 26

1. calculating risk in genetic counseling
2. planning population genetics based on carrier screening
3. determining carrier frequency in population.