Genetic Diseases Flashcards
How large (amino acids and KDa) is the CFTR protein?
1480 amino acids, molecular mass 168KDa
What is the structure of the CFTR gene? (Exon no., Kbp no.)
24 exons distributed over 250Kbp
What does the CFTR do?
Cystic fibrosis transmembrane conductance regulator functions as a chloride channel
What is the most common mutant allelic variant?
Delta F508
How common is this mutant allelic variant is Northern Europe?
70-80% prevalence
What is the mode of inheritance for CF?
Autosomal recessive
What is a nondisjunction?
An error in cell division, non separation of chromosomes
Can occur in mitosis or meiosis
What happens if nondisjunction occurs in meiosis 1?
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
What happens when nondisjunction happens in meiosis 2/II?
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
What happens if a gamete with n+1 fuses with a normal gamete?
A diploid zygote with a third copy of a chromosome - a trisomy.
Eg chromosome 21 trisomy causes Down syndrome
Most are lethal
What happens when a normal gamete fuses with a n-1?
Give a non lethal example
Monosomic zygote. The cell will have only one copy of a particular chromosome.
Eg. Turner syndrome - 1 X chromosome
Most are lethal
What happens when a haploid gamete fuses with a diploid?
Triploid
Lethal
But not in plants
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?
- aneuploid
- polyploid
What are OMIM databases?
Online Mendelian inheritance databases - list all known genetic disorders that exhibit Mendelian inheritance.
Give some recessive single gene disorders
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
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.
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.
Name some dominant single gene disorders
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
Marfan syndrome - __ in _____. Mutation in _____ gene - _____ protein. Leads to weakening of ______. Affects _____ + _____+______. Leads to _____ limbs. Death from _______.
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.
What are the two main classes do chromosome disorder?
Aneuploidies - number of chromosomes is altered
Structural alterations - translocations, deletions, inversions etc
___ % of all conceptions will have a chromosome disorder
Of these ___% will be a viable pregnancy
20
0.6
What are the 2 types of polypolidies?
A - fertilisation by 2 sperm or a diploid gamete
B - normal fertilisation, no cell division in mitosis
Why are monosomies and polysomies ( aneuploidies) of the X chromosome more common than the autosome ones?
Why are Y chromosomes tolerated?
- one chromosome is sufficient for viability as extra copies can be switched on or off.
- there are few essential genes on Y chromosome
What is Klinefelter syndrome? What is the birth incidence and karyotype?
X chromosome abnormality. Tall, intelligence issues, anger issues. Fertility problems.
1/1000 BI
Karyotype 47XXY
What are the karyotypes for male and female gender swapping and explain the mutation.
- 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.
What chromosome pair is Down syndrome trisomy on?
What are the main symptoms?
21
Low IQ, flat facial features, susceptibility to leukaemia, presentile dementia by 40
What chromosome is the Edward syndrome trisomy on? What are the symptoms?
What meiotic non disjunction causes it?
18
Maternal non disjunction at 1st meiotic division
Overlapping fingers, skull abnormalities, small chin, club foot, organ defects, death by 1 year.
What chromosome is patau syndrome trisomy on? What are the non disjunctions that cause it? What are the symptoms?
13 65% through maternal nondisjunction 20% through balanced translocation Cleft palate, scalp ear and heart defects 90% die within 1 year
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?
Balanced translocation - chromosome abnormality caused by rearrangement of parts between non homologous chromosomes.
