WEEK 16&17 - MODX LEC (INHERITED/NON INHERITED DISORDERS & MOLECULAR ONCOLOGY)

1. Dominant
2. Recessive

Inheritance pedigree that follows a (2) pattern:

Recurrent risk

the probability that an individual will develop a genetic disease

Heterozygous

One normal gene (wild-type) and one abnormal gene (mutation)

Homozygous

Inherited two genes with the same mutation

Cystic fibrosis

Gene on chromosome 7

Cystic fibrosis

Over 1300 mutations have been identified

Delta-F508

most common type of mutation in cystic fibrosis

Delta-F508

Three-base pair deletion

Sweat chloride test

Part of diagnosis for cystic fibrosis

Hereditary hemochromatosis

Excess iron absorption

Therapeutic phlebotomy

Treatment of hereditary hemochromatosis

HFE gene

hereditary hemochromatosis gene

1. Cystic fibrosis
2. Hereditary hemochromatosis

2 autosomal recessive disease:

1. Factor V leiden
2. Huntington's disease

2 autosomal dominant disease:

Factor V leiden

Hereditary hypercoagulability

1q23

Factor V gene is on chromosome ____

Oral contraceptives

Increase risk for thrombosis

1. Invader
2. PCR
3. RT-PCR (melting curve)

Factor V leiden mutation is detected by (3):

Huntington's disease

Late-onset neurodegenerative disorder

Heteroplasmy

Normal and mutated mtDNA copies

BRCA1

Risk for prostate and colon cancer gene

BRCA2

Risk for pancreatic cancer gene

1. Dominant
2. Recessive

Diseases with Mendelian Inheritance are either:

Punnett square

Pattern of inheritance are determined by:

1. Autosomal dominant
2. Autosomal recessive
3. X-linked pattern

Transmission patterns (3):

cystic fibrosis (CF)

Causes severe lung damage and nutritional deficiencies

Cystic fibrosis

Produces secretions that are too thick and sticky

Chromosome 7

Defective gene for cystic fibrosis

Chromosome 7

Codes for the cystic fibrosis transmembrane conductace regulator protein (CFTR)

Delta-F508

Deletion of phenylalanine

1. PCR (RLFP)
2. SS confirmation
3. Invader
4. Micro array
5. Direct sequencing

Detection of cystic fibrosis (5):

Sweat chloride test

Test for initial diagnosis of cystic fibrosis

Hereditary hemochromatosis

Over absorption of iron from the food

1. Pancreas
2. Liver
3. Skin

Accumulation of iron in the organs (3):

Hereditary hemochromatosis

Characterized by patients with heart disorders and diabetes

Hereditary hemochomatosis

HFE type 1, HLA gene product

1. C282Y
2. H63D
3. S65C

Common substitution of hereditary hemochromatosis, HFE gene (3):

C282Y (G to A)

Most common observed mutation in patients with hemochromatosis

Factor V Leiden (R506Q)

Mutation is 1691 Adenine to Guanine

1. Huntington's disease
2. Fragile X syndrome

Trinucleotide repeat (2):

Huntington's disease

Expansion of CAG

Mutable

Repeats of 28-35 _____

Reduced penetrance

Repeats of 36-39 _____

Repeats of 40 or greater

Repeats of ___ are associated with disease

George Huntington

discovered the Huntington's disease

Short arm of chromosome 4

Huntington's disease chromosome: ___

Hemizygous

Males will receive the mutated gene only from their mother and will be affected

1. Hemophilia A
2. Duchenne's muscular dystrophy
3. Fragile X syndrome

X-linked disease (3):

Duchenne's muscular dystrophy

Largest gene in the human genome with a length of 2.2 megabases

Dystrophin

Protein product in duchenne's muscular dystrophy

Duchenne Muscular Dystrophy (DMD)

Most common neuromuscular disorder

Fragile X syndrome

-X-linked dominant
-Disorder with reduced pentrance

Fragile X Syndrome (FXS)

Expansion of CGG

5-45

Normal range of CGG:

Fragile X syndrome

Inherited form of learning disability

Fragile X syndrome

-cytogenic abnormality of a breakpoint or fragile spot
-within telomere of a metaphase

FMR 1 gene

Fragile X syndrome is due to loss on function mutation in:

Mitochondria

16,569 base pairs
Containing 37 genes

1. Mutation on tRNA genes
2. Mutation on ribosomal RNA genes

Two mtDNA mutations that affect protein syntthesis:

Imprinting disease

Process of histone or DNA modification

Imprinting disease

Result in transcriptional silencing

Imprinting disease

Deletion of allele during egg and sperm production (gametogenesis)

Chromosome 15, del (q11q13)

Imprinting on chromosome ____

WEEK 17—-

WEEK 17: molecular oncology