Step 1 - Biochem 2

denniskwinn's version from 2015-04-25 15:56


Question Answer
Hardy weinberg population genetics1. Disease prevalence: p^2+2pq+q^2=1
2. Allele prevalence p+q=1
3. 2pq=heterozygote prevalence
4. Presence of x linked recessive disease in males =q, females = q*q
Hardy weinberg assumptions1. No mutations occur at the locus
2. No selection for any of the genotypes at the locus
3. Completely random mating
4. No migration
Prader willi and anglemans-Prader willi from deletion of normally active Paternal allele
-Angelmans from deletion of Maternal alleles
-Both Deletions=Chromosome 15
Prader willi characterizationMEntal retardations, hyperphagia, obesity, hypogonadism, hypotonia
Angelman’s syndrome characteristicsMental retardation, seizures, ataxia, inappropriate laughter (happy puppet)
Autosomal dominant-Often due to defects in structural genes. Many generations, both male and female, affected. Often pleiotropic and in many cases, present clinically after puberty.
-Family history crucial to diagnosis.
Autosomal recessive-25% of offspring from 2 carrier parents
-Often due to enzyme deficiencies
-Usually seen in only 1 generation
-Commonly more severe than dominant disorders; patients often present in childhood
X-linked recessiveSons of heterozygous mothers have 50% chance of being affected (no male to male transmission) - commonly more severe in males - homozygous females may be affected.
X-linked dominantTransmitted through both parents - either male or female offspring of affected mother may be affected while all female offspring of affected father are diseased - Example hypophosphatemic rickets
Mitochondrial inheritanceAll offspring of effected females may show signs of disease

Autosomal Dominant

Question Answer
Achondroplasia-Autosomal dominant
-Cell-signaling defect of FGF receptor 3.
-Results in dwarfism; short limbs, but head and trunk arc normal size.
- Associated with advanced paternal age.
Autosomal dominant polycystic kidney disease (ADPKD)-Formerly known as adult polvcystic kidnev disease. -Always B/L, massive enlargement of kidneys due to multiple large cysts.
-Patients present with flank pain, hematuria, hypertension, progressive renal failure.
- 90% of cases are due to mutation in APKD1 (chromosome 16; 16 letters in "polycystic kidney"). -Associated w/polycystic liver disease, berry aneurysms, mitral valve prolapse, infantile form is recessive.
Familial adenomatous polyposis-Autosomal dominant, colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected.
-Mutation on chromosome 5 (APC genes)
( 5 letters in polyp)
Familial hypercholesterolemia (hyperlipidemia type IIA)Autosomal dominant
-Elevated LDL due to defective or absent LDL receptor.
-Heterzygotes (1:500) have cholesterol of 300mg/dL, homozygotes (very rare) have 700+mg/dL, severe atherosclerotic disease early in life and tendon xanthomas (A`chilles)
- MI may develop before age 20
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)Autosomal dominant Inherited disorder of blood vessels. Findings: telangiectasia, recurrent epitaxis, skin discoloration, AV malformations
Hereditary spherocytosis-Autosomal dominant
- Spheroid RBCs due to spectrin or ankyrin defect → hemolytic anemia
- ↑MCHC, splenectomy is curative (for the hemolysis)
Huntingdon’s disease-Autosomal dominant trinucleotide repeat disorder
- Gene 4 location CAG repeats.
-Findings: depression, progressive dementia, choreiform movements, caudate atrophy, ↓GABA and ACh in brain. Sx manifest b/w 20 and 50y
(Hunting 4 food)
Marfan’s syndrome-Autosomal dominant
-Fibrillin gene mutation→ connective tissue disorder affecting skeleton, heart and eyes. Tall w/long extremities, pectus excavatum, hyperextensive joints and long, tapering fingers and toes (arachnodactyly), cystic medial necrosis of aorta→aortic incompetence and dissecting aortic aneurysms; floppy mitral valve - subluxation of lenses
Multiple endocrineneoplasia-Autosomal dominant syndromes characterized by familial tumors of endocrine glands
- MEN2A and B associated with ret gene(RB)
Neurfibromatosis 1 (von RecklingHAUSEn’s disease)-Autosomal dominant

Café au lait spots
Axillary freckling
Eye- Lisch nodules

Skeletal bowing
Positive family history
Optic Tumor

-On long arm of chromosome 17; (17 letters in von Recklinghausen)
Neurofibromatosis 2Autosomal dominant:
MISME Too is
M - Multiple
I - Inherited
S - Schwannomas (vestibular and spinal)
M - Meningioma
E - Ependymoma
-NF2 gene on chromosome 22
- (type 2=22)
Tuberous sclerosis-AD

Tu=tuber calcification(of the perivent) and tumor (malig astrocytoma)
B= blood in urine(hematuria)
E=eye...retinal mulberry
R= rhabdomyoscarcoma
O=off white skin (ash,hypo-pigmented skin lesions)
U=sub-Ungual fibromas
S=shagreen and sebaceous adenoma..
(the t and the s ..the beginning and the end are double letters)
Von Hippel-lindau disease-Autosomal dominant
Hemanigoblastomas(eye, cerebellum, medulla)
Increased renal cancer(RCC)
Port-wine stains
Eye dysfunction
Liver, pancreas, kidney cysts
· Bare bones version: Hippel-Lindau, with H and L as above.
-A/w with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p)→ constitutive expression of HIF transcription factor and activation ofangiogenic GFs
- Von Hippel Lindau = 3 words = chromosome 3