L4 Flashcards
Example of mendelian/mongenic and polygenic trait?
- Mendelian/monogenic: ABO blood group
2. Polygenic: adult stature
Compare mendelian and non-mendelian genes
Mendelian Involving a single locus Give characteristic inheritance patterns DNA changes are almost always Mendelian they are either present or not Non-Mendelian Factors determined by multiple genes (2+) or influenced also by environment -> multifactorial inheritance Dichotomous characters either have character or do not loci are considered susceptibility genes Quantitative/continuous characters trait shows phenotype range that is continuous
Proband (propositus/proposita)
- individual who brought the family to the attention of scientists
Individuals are labeled by generation (Roman numerals) and from left to right (Arabic numerals)
a
Autosomal dominant
affected person has an affected parent
transmitted by either sex
affected person has 50% chance of passing on disease to offspring
Usually due to gain of function or novel function of gene (neomorphic mutation)
Autosomal dom
Huntington Disease 1/10,000
late onset, involuntary movements, dementia
Myotonic Dystrophy 1/8,500
prolonged muscle contraction (myotonia), muscle atrophy, cataracts
Neurofibramomatosis, type I 1/4,000-5,000
tumours on the peripheral nerves of the head, neck and body; pigmented café-au- lait spots
Autosomal recessive
individuals usually born to unaffected parents
parents are unaffected carriers
affects either sex
requires inheritance of 2 defective alleles
– may be the same or different
usually due to loss of gene function
Autosomal recessive
cystic fibrosis ~1/2,000
recurrent lung infections, infertility in males
phenylketonurea (PKU) 1/2,000-5,000 in Europeans
Intellectual disability
Defect in ability to digest phenylalanine
-thalassemia
1/20,000 in general population; 1/100 in areas
where malaria is endemic
– severe anemia (depletion of red blood cells)
Tay-Sachs disease 1/3,000 in Ashkenazi Jews
– neurological degeneration, blindness, paralysis
X-linked recessive disorders
Duchenne muscular dystrophy males 1/3,500
early onset, progressive muscle weakness, severe skeletal muscle degeneration
Haemophilia A males 1/5,000
deficiency of clotting factor VIII, excessive bleeding from minor traumas, internal bleeding
Fragile X syndrome
males 1/1,500, females 1/2,500
Intellectual disability
mildly affects 1/3 of female carriers- appears partially dominant
X-linked dominant
affected fathers pass disorder to daughters,
never to sons
Child of affected female has 50% of getting disorder
vitamin D-independent rickets
quite rare
Y linked
Affects only males
Affected males always have an affected father (unless it was a spontaneous mutation)
Y-linked disorders are very rare- often involve male sexual Development; also one form of retinitis pigmentosa is suggested to be Y-linked
X inactivation
- Definition of X linked gets blurred in females due to X inactivation
- Female carriers for recessive disorder may manifest the phenotype
- Heterozygous females for x-linked dominant disorder usually less severely affected than males
- Severity of defect depends on disorder
a) E.g. Hemophilia - circulating blood products are averaged with normal product (intermediate phenotype)
b) in contrast – local defect– if normal x is inactivated in a specific tissue where the product is need, get severe defect (=manifesting heterozygotes)
Locus heterogeneity
a single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci (often leads to genetic complementation).
Examples:
Deafness
polycystic kidney disease (e.g., PKD1 and PKD2)
retinitis pigmentosa (RP)
Example: RP has autosomal dominant, autosomal recessive, and X-linked origins. However, only one mutant locus is needed for the phenotype to manifest.
