genetic disease Flashcards
what is penetrance?
proportion of those that carry the gene will express the trait.
what is expressivity?
how the gene is expressed in an individual with same mutation
what is a disorder caused by single genes with large effects?
cystic fibrosis and sickle cell anaemia.
what type of disorder will be caused by chromosomal disorders?
Downs syndrome.
What are complex multigenic disorders?
- gene variants.More than one gene or mutation within a gene associated with conditions.
- each variant has low penetrance and small effect.
what are single nucleotide polymorphisms (SNPs)?
change in one nucleotide pair
What are contiguous repeats?
dinucleotides
tri (3)
tetra (4)
what is a silent mutation?
no change in amino acid sequence
what is missense?
change in amino acid sequence
what is a nonsense mutation?
premature stop codon
what is an amino acid sequence that changes but retains biochemical properties called?
conservative
what is the amino acid sequences that is changed but changes biochemical properties?
non conservative.
what is frameshift mutation caused by?
insertion and deletion unless it is insertion or deletion of 3 nucleotides.
when is a disorder not X-linked?
when passed on from male to male
when is a disorder not mitochondrial?
when passed on from male.
what does autosomal dominant mutation have?
- variable expressivity despite high penetrance.
- may also have incomplete penetrance
what are the key features of autosomal dominant inheritance?
- males and females equally affected.
- unaffected persons do not pass on trait.
- vertical pattern of inheritance with affected individuals in multiple generations.
in autosomal dominant inheritance why are homozygotes more severely affected?
there is variable expressivity.
what type of disorder or mutation is Marfan’s syndrome caused by?
70-80% autosomal dominant with the remainder De Novo mutations (dna polymerase)
in what gene does the mutation for the syndrome occur?
gene FBN1
what does Marfan’s syndrome cause to the eye?
Ectopia Lentis slipping of the lens due to weakness of the cilliary zones.
what are the key features of autosomal recessive diseases?
- males and females equally affected.
- disorder usually transmitted by two unaffected carrier parents.
- horizontal pattern of inheritance.Found in consanguineous families.
How is Stargardts Macular Dystrophy caused?
- ABCA4 mutations
- causes change in ATP binding cassette
- phototransduction cycle affected
- Toxic vitamin A build up in RPE
- Lipofuscin build up.
what are the features of x-linked recessive?
- affected males do not transfer to son
- hemizygous males and homozygous females are affected fully.
- vertical transmission of inheritance
- variable expressivity
what is lyonization?
in females one x chromosome is inactivated and it could be the healthy one.
What is multifactorial inheritance?
incidence of siblings being affected is less than if you have classic mendalian inheritance.
need other environmental factors and mutations.
what do structural changes in chromosomes result in?
- rearrangements
- loss of part of chromosome.
what do most people who have downs syndrome have it due to?
robertsonian translocation.
what are isochromosomes?
chromosomes split in a wrong way
what are ring chromosomes?
chromosomes bind and form a ring.
what are chromosomal aberrations?
- translocations
- Isochromosomes
- Deletions
- Inversions
- Ring Chromosomes.
what are the ocular complications for down’s syndrome?
- refractive errors common
- Hyperopia
- Astigmatism
- Strabismus
- cataracts
- Nystagmus
- Reduced accomodation
What does the Fragile X CGC tri-nucleotide repeat in UTR of FMR1 gene lead to?
altered connectivity in CNS leads to mental retardation.
What does Leber’s hereditary Optic Neuropathy cause?
- cells with high metabolic demand are affected first
- Optic nerve damage
- Affects mtDNA
what is an association study?
not families but populations with and without a disease.
How is the Genome Wide Association study done?
- Uses arrays that contain immobilised allele.
- fragmented DNA is fluorescently tagged.
- allowed to hybridise
- fluorescent signal present on SNP chip signifies binding.
