Molecular Genetics Flashcards
Describe telomers in humans.
repeats of 5’- TTAGGG -3’ (10-15 thousand bps) at end there is a long end overhang without a complimentary sequence that loops back on itself to form a complex structure
Why are telomers required?
because lagging strand synthesis at the end of the chromosome requires a free 3’-hydroxyl group to elongate from, but there is not room for a new RNA primase sometimes, so one DNA molecule per replication would be lost at the end of the chromosome
When is telomerase expressed?
most somatic cells in mammals do not make telomerase (so the telomeres get shorter every cell division and cells will only divide a limited number of times and the amount of divisions decreases as we age)
Tumor cells DO express telomerase, though, and cancer cells replicate indefinitely
anomalies in pigmentation of finger nails
premature graying
bone marrow failure
liver cirrhosis
lung scarring
somewhat shortened lifespan (median age at death >50 years)
Dyskeratosis congenita
AD
het loss of RNA component of telomerase
What is the first line of defense for DNA repair?
proofreading by DNA polymerase (3’ to 5’ exonuclease)- the next nucleotide will not be added unless there is good base pairing at the new 3’ end, if not, the incorrectly paired base at 3’ is removed
(highly accurate, but not perfect)
Name the mismatch repair enzymes and what condition(s) are caused by mutations to these enzymes.
MLH1, MSH2, MSH6, and PMS2
Lynch syndrome
What genetic disease is associated with loss of BER function?
mutations in MUTYH (which produces a specific glycosylase)
AR form of colorectal polyposis with increased colon cancer risk
Describe the special case of 5’-methyl C.
Deamination of C gives U, but deamination of methylated-C (which is important in turning off gene expression) gives a T - this leads to TG base pair that is repaired by a unique glycosylase (through BER) that is inefficient (results in 1/3 of single gene bp mutations) causing mutation hot-spots in these highly methylated regions that are not easily repaired
What genetic diseases are associated with defects in NER?
Xeroderma pigmentosum
Cockayne syndrome
UV sensitivity- photophobia keratitis atrophy of the skin lids Increased risk of cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma) Variable expressivity
Xeroderma pigmentosum
AR
7 different genes (damage recognition- APC, XPE, XPA, helicase- XPB, XPD, nuclease- XPF, XPG) associated with NER (loss of function results in inability to repair DNA with NER)
What causes double stranded breaks?
ionizing radiation
replication errors
oxidative damage
metabolic processes
cerebellar ataxia oculomotor apraxia choreoathetosis telangiectasias of the conjunctivae immunodeficiency (frequent infections) increased risk for malignancy (esp. leukemia, lymphoma)
ataxia-telangiectasia
AR
due to loss of signal that double strand breaks are present and repair is necessary
What genetic conditions/genes are associated with homologous recombination repair?
BRCA1, BRCA2
BARD1, BIRP1, NBN
Describe how methylation in early embryonic development is different for imprinted genes vs most genes.
for most genes DNA methylation is removed around fertilization (allows for early embryonic cells to be totipotent) and re-methylation occurs around the time of implantation
for imprinted genes, de-methylation/re-methylation occurs during gametogenesis prior to fertilization (establishes parent of origin methylation patterns)
hypotonia
developmental delay hypogonadism
mild ID
initial difficulty feeding with progression to hyperphagia later in childhood
Prader Willi syndrome
15q11-13 imprinting disorder (missing information from the paternal copy of the gene)
