Genetic Diseases

Question 0

How large (amino acids and KDa) is the CFTR protein?

Answer 0

1480 amino acids, molecular mass 168KDa

Question 1

What is the structure of the CFTR gene? (Exon no., Kbp no.)

Answer 1

24 exons distributed over 250Kbp

Question 2

What does the CFTR do?

Answer 2

Cystic fibrosis transmembrane conductance regulator functions as a chloride channel

Question 3

What is the most common mutant allelic variant?

Answer 3

Delta F508

Question 4

How common is this mutant allelic variant is Northern Europe?

Answer 4

70-80% prevalence

Question 5

What is the mode of inheritance for CF?

Answer 5

Autosomal recessive

Question 6

What is a nondisjunction?

Answer 6

An error in cell division, non separation of chromosomes

Can occur in mitosis or meiosis

Question 7

What happens if nondisjunction occurs in meiosis 1?

Answer 7

Both chromosomes of a pair migrate to the same pole, leaving one daughter cell without a chromosome
Gametes have unusual numbers of chromosomes
Two have 1 extra - n + 1
Two lack 1 - n - 1

Question 8

What happens when nondisjunction happens in meiosis 2/II?

Answer 8

Both sister chromatids of a chromosome migrate to the same pole of the cell. Therefore one chromosome separates abnormally, resulting in two abnormal cells.
2 normal gametes
1 gamete n-1
1 gamete n+1

Question 9

What happens if a gamete with n+1 fuses with a normal gamete?

Answer 9

A diploid zygote with a third copy of a chromosome - a trisomy.
Eg chromosome 21 trisomy causes Down syndrome
Most are lethal

Question 10

What happens when a normal gamete fuses with a n-1?

Give a non lethal example

Answer 10

Monosomic zygote. The cell will have only one copy of a particular chromosome.
Eg. Turner syndrome - 1 X chromosome
Most are lethal

Question 11

What happens when a haploid gamete fuses with a diploid?

Answer 11

Triploid
Lethal
But not in plants

Question 12

Plants:
What are cases which the chromosome number differs from normal by just a few?

What are cases where extra complete sets of chromosomes exist?

Answer 12

• aneuploid

- polyploid

Question 13

What are OMIM databases?

Answer 13

Online Mendelian inheritance databases - list all known genetic disorders that exhibit Mendelian inheritance.

Question 14

Give some recessive single gene disorders

Answer 14

Albinism
Ataxia telangiectasia - degeneration of nervous system
Bloom syndrome - dwarfism, rash, cancer
Cystic fibrosis
Fanconi anemia - slow growth, heart defects, leukaemia
Galactosemia - galactose in liver, retardation
Phenylketonuria - mental retardation, accumulation of phy
Sickle cell anaemia
Thalassemia - improper haemoglobin
Xeroderma pigmentosum - skin cancer, death
Tay-Sachs disease - improper gangliosides metabolism in nerve cells, early death

Question 15

PKU - affects __ in _______live births. Mutation in _______ enzyme. Leads to ________ within 30 days of birth. Less/more pigmented than siblings. Managed by restricting ____ in diet during childhood and pregnancy.

Answer 15

PKU - affects 1 in 12000 live births. Mutation in phenylalanine hydroxylase enzyme. Leads to permanent brain damage within 30 days of birth if untreated. Less/more pigmented than siblings. Managed by restricting Phe in diet during childhood and pregnancy.

Question 16

Name some dominant single gene disorders

Answer 16

Achondroplasia - dwarfism
Brachydactyly - malformed hands, short fingers
Camptodactyly - stiff bent little fingers
Crouzon syndrome - defective face - protruding eyes
Ehlers danlos syndrome - connective tissue disorder
**Familial hypercholesterolemia - elevated cholesterol
Poly cystic kidney disease - cysts on kidneys
Huntington disease - degeneration of nervous system
Marian syndrome - connective tissue defect, death by aortic rupture
Nail patella syndrome - absence of nails and kneecaps

Question 17

Marfan syndrome - __ in _____. Mutation in _____ gene - _____ protein. Leads to weakening of ______. Affects _____ + _____+______. Leads to _____ limbs. Death from _______.

Answer 17

Marfan syndrome - 1 in 10,000. Mutation in FBN1 gene - fibrillin protein. Leads to weakening of connective tissue. Affects skeletal system , eyes and cardio system. Leads to tall, long limbs. Death from aortic rupture.

Question 18

What are the two main classes do chromosome disorder?

Answer 18

Aneuploidies - number of chromosomes is altered

Structural alterations - translocations, deletions, inversions etc

Question 19

___ % of all conceptions will have a chromosome disorder

Of these ___% will be a viable pregnancy

Answer 19

20

0.6

Question 20

What are the 2 types of polypolidies?

Answer 20

A - fertilisation by 2 sperm or a diploid gamete

B - normal fertilisation, no cell division in mitosis

Question 21

Why are monosomies and polysomies ( aneuploidies) of the X chromosome more common than the autosome ones?
Why are Y chromosomes tolerated?

Answer 21

• one chromosome is sufficient for viability as extra copies can be switched on or off.
• there are few essential genes on Y chromosome

Question 22

What is Klinefelter syndrome? What is the birth incidence and karyotype?

Answer 22

X chromosome abnormality. Tall, intelligence issues, anger issues. Fertility problems.
1/1000 BI
Karyotype 47XXY

Question 23

What are the karyotypes for male and female gender swapping and explain the mutation.

Answer 23

• Karyotype 46 XX phenotype male
  Two X chromosomes but part of the Y chromosome translocated onto the X
• karyotype 46XY phenotype female
  Genetically male but insensitive to testosterone which is needed for male development, therefore develop as females.

Question 24

What chromosome pair is Down syndrome trisomy on?

What are the main symptoms?

Answer 24

21

Low IQ, flat facial features, susceptibility to leukaemia, presentile dementia by 40

Question 25

What chromosome is the Edward syndrome trisomy on? What are the symptoms?
What meiotic non disjunction causes it?

Answer 25

18
Maternal non disjunction at 1st meiotic division
Overlapping fingers, skull abnormalities, small chin, club foot, organ defects, death by 1 year.

Question 26

What chromosome is patau syndrome trisomy on? What are the non disjunctions that cause it? What are the symptoms?

Answer 26

13
65% through maternal nondisjunction
20% through balanced translocation
Cleft palate, scalp ear and heart defects
90% die within 1 year

Question 27

What type of translocation would be expected if there is a family history of DS or trisomy 13 associated with failed pregnancies or young mothers?

Answer 27

Balanced translocation - chromosome abnormality caused by rearrangement of parts between non homologous chromosomes.