Term
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Definition
| Mutations in different genes lead to the same phenotype |
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Term
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Definition
| Different mutations in the same gene lead to the same phenotype |
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Term
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Definition
Autosomal Recessive
Homogentistic Acid oxidase deficiency
Phe -> Tyr
Bluish blackish discolration of the eyes, ear, urine. |
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Term
| Oculocutaneous albinism OCA1 |
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Definition
Tyrosinase deficiency.
Inability to convert tyrosine to melanin
Locus heterogeneity. Most types are Autosomal Recessive |
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Term
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Definition
Deficiency of CBS
Autosomal recessive
Mental Retardation, fits, osterperosis |
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Term
| Maple Syrup Urine Disease |
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Definition
Autosomal recessive
Deficiency of branched-chain ketoacid decaboxylase.
Val, Leu, Ile are excreted.
1/200 in PA Mennonites |
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Term
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Definition
Deficiency of galactose-1-phosphate
Autosomal Recessive
Presents 2nd week. Vomiting, lethargy, jaundice.
Prevented by galactose/lactose free diets.
Guthrie test confirms |
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Term
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Definition
Hepatomegally.
Autosomal Recessive
Type1(von gierke): Deficiency of glucose 6-phosphatase. Effects liver(low blood sugar)
Type II(Pompe): Deficiency of a-1,4 glucosidase: Primarliy effects muscle. |
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Term
| Glucose-6-phosphate dehydrogenase (G6PD) deficency |
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Definition
X-linked. Common in Africans
Most common enzyme deficiency
Usually presents as drug-induced hemolysis |
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Term
| Congenital Adrenal Hyperplasia(CAH) |
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Definition
Steroid 21-hydroxylase deficiency
Autosomal recessive
Lack of negative feed back contro lfo ACTH -> Salt wasting.
usually result of recombination between pseudo gene and CYP21.
classic- severe enzyme deficiency prenatal onset. |
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Term
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Definition
Autosomal Recessive
Deficiency of B-glucosylceramidase
Severity related to residual enzyme activity.
Enzyme therapy works well for type 1: Cerezyme |
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Term
Disorders of Porphyrin metabolism
(heme biosynthesis)
(exceptions to AR patern of blood diseases) |
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Definition
Acute Intermittent Porphyria(AIP)
AD, Haploinsufficieny of
porphobilinogen deaminase. Latent until puberty
Congenital Erythropoietic Porphyria (CEP): AR with photosensitivity
Variegate Porphyria(VP):
Founder effect amongst Afrikaaners. Photosensitivity |
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Term
| Immunogenetics: Self recognition HLA genes |
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Definition
Class 1:
HLA-A and HLA-B important for tissue
matching >500 alleles
Class 2:
HLA-DR important for tissue matching
>300DRB alleles
Each type of immunoglobin gene is assembled by DNA rearrangements that occur specifically in B lymphocytes.
Somatic change not germline |
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Term
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Definition
Collect DNA samples from affected individuals and their families.
10 informative meiosis(20 for recessive disorder) required.
Type each DNA sample for markers spread over the entire genome(except for x-linked)
Each marker is assessed to determine whether it is lose to the gene mutated in affected individuals |
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Term
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Definition
Lod score +3, p=0.05 (Likelihoodratior 1:1000) Indicative of linkage
Lod score -2 or lower, linkage exluded
Haplotyping then determines region a gene is in using markers.
SSCP Analysis of each exon in each gene.
Sequence the gene. Make sure mutations are not observed in control individuals. |
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Term
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Definition
| In a consanguineous recessive pedigree, affecteds are homozygous for the same mutant allele and for nearby marker alleles |
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Term
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Definition
Only sequence Exons.
Useful when linkage isn't feasible:
Disease isnt transmitted
locus heterogeneity
unclear inheritance pattern
Kabuki syndrome was found this way |
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Term
| Review of gene identification methods |
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Definition
Positional: Use only genetic information
Linkage and recombination
Breakpoint: Genes disrupted by
chromosomal translocations
Exome Sequence: Uses only sequence
information. No linkage/biology |
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Term
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Definition
AR disease becomes more common
Ashkenazi jews: Tay-Sachs, Gaucher,
Dysautonomia |
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Term
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Definition
Sickle cell disease and a/b thalassaemia
Both AR. Resist Malaria
G6PD: X-linked. Mediteranean. Malaria
Non-insulin diabetes: periodic starvation |
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Term
| Tricks in autosomal recessive CARRIER'S CHANCES |
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Definition
Reference P-square
Sibling of an affected has 2/3 chance of carrying
Sibling of carrier (i.e.aunt/uncle of affected) have a HALF 1/2 chance
-why? previous generation was probably AAxAa since no one was affected before that--chance of 'a' being passed on is 1/2 |
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