lecture 14 Flashcards
What is hemizygous?
Having one copy of gene (Males are hemizygous for X chromosome)
What are genes in Y chromosome responsible for?
spermatogenesis
What is psudoautosomal region?
regions of X and Y chromosomes that match, and they line up chromosomes correctly during meiotic recombination.
Characterstic of X-linked recessive disorder (4)
- more common and more severe in males
- Skipped generations common
- L-shape (affected male > carrier female > affected male)
- No male to male transmission
What happened if females get disorder for X-linked recessive disorder?
That means that female has skewed X inactivation.
Transmission of Glucose 6-phosphate dehydrogenase (G6PD) deficiency
X-linked recessive disorder
Transmission of Duchenne muscular dystrophy
X-linked recessive disorder
transmission of hemophilia A and B
X-linked recessive disorder
Transmission of Lesch-Nyhan syndrome
X-linked recessive disorder
What is Lesch-Nyhan syndrome?
Hypoxanthine guanine phosphoribosyl transferase deficiency, which results in hyperuricemia, gout, self mutilation
transmission of red-green color blindness
X-linked recessive disorder
transmission of SCID (2)
Autosomal recessive and X-linked recessive
mutation in different gene results in same disease
Chracteristics of X-linked dominant disorder(5)
- Skipping of generation not common
- Preponderance of females compared to males
- No male to male transmission
- Variable expressivity in females due to phenomena of X-inactivation.
- lethal for males
Characteristics of Y-linked inheritance(2)
- Only males show the trait
- Mutation leads to sterility and are not passed on.
- Male transmit to all their sons
Example of Y-linked inheritance
- Various mutations in SRY genes
- H-Y histocompatibility antigen
- Hairy ears
What is SRY gene?
Determine if the person is male or female. So if mutation is on SRY gene, even though person has Y chromosome, mutation leads to development of female characteristics.
What can complicate an autosomal dominant pedigree?
Reduced or incomplete penetrance
What is characteristic of incomplete penetrance?
1 Skipped generation
What is locus heterogeneity?
Mutations at different loci (different genes) that cause the same disease phenotype
Example of locus heterogeneity(5)
- Osteogenesis imperfecta
- Sensorineural hearing impairment
- Retinitis pigmentosa
- Charcot marie Tooth disease (AD,AR,X-linked)
- SCID (AR and X-linked)
What causes osteogenesis imperfecta?
Defect in collagen caused by mutation on chromosome 17 or chromosome 7
What is variable expression?
Individuals who have inherited same mutant allele, some individuals are severely affected and other are mildly affected.
3 reasons for variable expression
- Random chance
- Other genetic factors (modifier loci) or sex influence
- Environmental exposure
How is variable expression explained in hemochromatosis?
Due to sex difference, male has more severe disorder than female, because female release iron through mentruation, reducing iron concentration in the blood.
Mode of transmission for xeroderma pigmentosum
autosomal recessive
De novo mutation
mutation is transmitted from an unaffected parent to an affected offspring. (usually on hotspot for mutation)
Example of de novo mutation
- Neurofibromatosis (NF1)
- Achondroplasia
- Duchenne muscular dystrophy (about 33% is de novo)
- Osteogenesis imperfecta,
- Marfan syndrome
The relationship between paternal age and de novo autosomal dominant mutation
Higher paternal age, higher chance of de novo autosomal dominant mutation.
Characteristic of denovo mutation pedigree
2 skipped generation for autosomal dominant mutation
When does de novo mutation occur?
During gamete formation, which is not in the parents original genome.
When could de novo mutation for X-linked recessive occur?
in single sperm from dad or
in single ovum from mom or
in fertilized egg occuring soon after conception
How is germline mosaicism different from de novo mutation?
For new mutation, there is a single child with a disorder and no family history of the disorder, but for germline mosaicism, more than 1 are affected, parents should shoe mutation in their germline but normal peripheral cells.
Examples of disease that shows delayed age of onset(3)
- Huntington disease
- Hemochromatosis
- Familial breast cancer
