lecture 2 and 3 (autosomal and recessive inheritence)

principle of segregation

genes on chromosomes segregate during meiosis and they are transmitted as distinct entities from one generation to the next

allele frequency

how often a particular gene sequences occurs in a population

genotype frequency

how often a given genotype occurs in a population

characteristics of autosomal dominant inheritance

• 2 sexes exhibit trait in equal ratios

• no skipping of generations=vertical transmission

• father to son transmission of the disease gene is present

• affected heterozygote transmits the disease causing allele to half of their children

occurence risk

probability of producting an affected child when no children have been affected

recurrence risk

probability that a couple with an affected family member will produce another child that is affected

MOI for Achondroplasia

autosomal dominant g

gene mutation for achondroplasia

point mutation in the 380th codon of FGFR-3 gene

symptoms of achrondroplasia

short limbed dwarfism, characteristic faces and radiological features of the spine

incidence of achondroplasia

1/10,000

neurofibromatosis MOI

autosomal dominant

Gene mutation for neurofibromatosis

cafe au lait spoits, fibromatous skintumours and increased risk of malignant tumors

MOI for condition that affects retinal pigment epithelium via mutation is bEST1 gene

autosomal dominant

vitreoretinochoroidopathy gene mutation

BEST1, encodes Ca activated cl channel

symptoms of vitreoretinochoroidopathy

highly pigmented circular band in outer region of retina, occular anomalies, microcornea

BRCA 1 mutation display what patterns of inheritence

locus heterogeneity, age dependent penetrance, and anticipations

MOI of huntingtons

HTT gene

what gene is affected for huntingtons

HTT gene due to expansion of CAG trinucleotide repeats in coding region

symptoms for huntingtons

progressive neurological disorder resulting in motor cognitive and psychiatric disturbances

characteristics of autosomal recessive interitance

• observed in siblings but not earlier generations

  • males and females affected equally

quasidominant inheritence

mimis autosomal dominant pattern despite being auto recessive (when a homo and hetero mix)

MOI for hypophosphatasia

autosomal recessive

gene for hypophosphatasia

alkaline phosphatase, ALPL (role for bones and teeth)

symptoms of hypophosphatasia

weak and soft bones, skeletal abnormalities like rickets , poor feeding, failure to thrive

hypophosphatasia patterns of inheritence

variable expression and pliotrophy

hurler syndrome MOI

autosomal recessive

gene for hurler syndrome

a-L-iduronidase (break down GAGs)

hurler syndrome symptoms

buildup of GAGS in lyososomes

• skelatal abnormalities, short stature, intellectual disability, corneal clouding

cystic fibrosis affected gene

CFTR gene mutatuon (encodes for cl channel) affect sweat musuc and disgestive enzymes

CF MOI

autosomal recessive

patterns of inheritence for CFTR

pleiotrophy

genetic drift

high variation in frequency of different genotypes found in smaller populations.

founder effect

because of genetic drift, diseases that are otherwise uncommon may be seen fairly frequently in a small population

Ellis van crevald syndrome

due to genetic drift in amish community

• reduced stature, polydactyly, congenital heart defects

de novo mutation

genetic disease in absense of family history (normal allele changes to disease causing allele)

examples of de novo mutations

achondroplasia, neuofibromatosis 1, marfan syndrome

• alot of autosomal dominant

germline mosaicism

1 parent in embryonic development gets a mutation affecting part of the germline but few to no somatic cells

parent can test negative for disease or carrier but can transmit mutation ot offspring

complications with germline mosaicism

alters recurrence risk estimates

example of germline mosaicism

duchenne muscular dystrophy ( x linked recessive,gene L37)

• unaffected parent can carry dystrophin mutation in germ cells and then can still be transmitted

reduced penetrance

individual carries disease causing allele but does not express disease

examples of reduced penetrance

retinoblastinoma

fragile x syndrome (carrier can be unaffected or mildly affected when carrying)

age dependent penetrance or delayed age of onset

delayed onset of genetic disease (breast/ovarian cancer, huntingtons, alzheimers)

variable expression

disease severity varies greatly between individuals, those with mild expression cna still transmit to child and child can have severe expression of the disease

example of variable expression

twins with NFT1 (one is worse than the other)

plieotrophy

genes exert effects on multiple aspects of physiology or anatomy

example of plieotrophy

hypophosphatasia

• wek bones and teeth and uterine anomalies

locus heterogeneity

single disease phenotype can be caused by mutations at different loci on different genes

ex. breat cancer on BRCA 1 and 2

anticipation

disease displays an earlier age of onset and severe expression in more recent generations of a pedigree

examples:BRCA 1/2, huntingtons, fragile x

• basically a mom will get breast cancer later in life than her daughter will get

consanguinity

reproductive relarionship shared by blood relatives