Block I Flashcards
In the miller-urey exp. that sougth to explain how organic compounds formed under prebiotic conditions, voltage was applied to mix of methane, ammonia, water and hydrogen. Which compounds were found in the condensate that resulted from this procedure?
adenine, fatty acids, glycine, hexases. NOT RNA, amino acids, carboxylic acids, nucleic acid bases, sugars
genetic deficiency of what enzymes results in alkaptonuria?
homogentisic acid oxidase
What sequence motifs might you expect to be present in a protein that activates a gene at the chromosomal level during fetal development?
DNA binding motif; homeodomain
what is the diff btw an ortholog and a paralog?
ortholog: two homologous genes in the different organism/species
paralog: two homologs from the same species
what is the appox. percentage of the humane genome represented by Alu sequences?
13%
What is the approx. percentage of the human genome represented by coding sequences?
2%
What is the approx. percentage of the human genome represented by LINE sequences?
20%
What is the approx. pecentage of the human genome represented by satellite DNA?
13%
what is the approx. percentage of the human genome represented by singl-copy sequences?
45%
what is the approx. percentage of the human genome represented by non-coding repetitive sequences?
55%
What are the sizes, roughly, of alpha satellites, lines, sines, microsatellites, minisatellites?
microsatellites: 1-13 bp alpha-satellites- 171 bp mini satellites 14-500 bp SINE 90-500 bp LINE 900-7000 bp
What is the name for chromosomal regions, a few kb in length, that are repeated in a dispersed fashion on the same or different chromosomes?
segmental duplications
How big is the haploid human genome?
3 billion base pairs (3,000,000)
What are some mechanisms that give rise to psuedogenes?
deleterious mutations of the promotor or coding sequence so that gene expression is not possible.
2. processed pseudogenes- have no intron. some pseudogenes arose from reverse transcription of processed mRNAs into cDNAs, which were re-integrated into a random location in the human genome .
What is horizontal gene transfer?
transfer of genes from the genome of one species into ththat of another
What is a nucelosome?
a nucleosome consists of some DNA wrapped around a histone protein core
how big is the “beads on a string” DNA structure?
10 nm
Put these terms in order of size: chromatid, coils, metaphase chromosome, rosette, 30nm fiber
30 nm fiber, rosette, coil, chromatid, metaphase chromosome
What DNA repeat element protects a chromosome from being inserted into another chromsome through random recombination?
telomere
What does the ARS1 sequence do in a YAC?
It is responsible for helping the YAC replicate during the S-phase cell cycle. Think of it as the origin of replication!
In what cell cycle phase do cells prepare for DNA synthesis?
G1
Where do we see high GC content?
in regions of the chromosome that are gene-rich
What are the characteristics of chromosomes stained with Q-banding?
Similar patter to G-banding (heterochromatin dark, euchromatin light), but requires fluorescent microscope
What is R-banding?
heat-denatured chromsomes that are then steined with giemsa give a patter that is opposite of typical G-stains
What is C-banding?
a type of stain where chromosomes are treated with base before giemsa staining to show the chromatin near the centromeres
how does a chromosome preparation obtained early in metaphase differ from one obtained during late metaphase after G-banding?
in the prometaphse prep, the chromsomes appear longer and the banding resolution is higher
what do we call chromsomes 13,14,15,21,22?
acrosomic chromosomes
What are some common clinical complications of Down’s syndrome?
cardiac septal defects, cataracts, duodenal atresia, myeloid leukemia, early onselt Alzheimers
A couple has a child with Down’s syndrome who has a karyotype of 47,XY,+21. The probability for their next child to have Downs is _
1%
What is the name for the genotype 47,XXY? What are some clinical manifestations?
klinefeller: hypogonadism with small testes, tall stature and long extremities, gynecomastia, less body hair/muscle mass, infertility, some behave probs and learning disabilities
What are some clinical manifestations of 47,XYY?
tall stature, long extremities, some behavioral probs/learning disabilities. NO INFERTILITY.
What are some clinical manifestations of 47,XXX?
decreased ferlitiy, menstrual instability, slight developmental probs.
What is the name of the genotype for 45,X? Clinical manifestations?
turner’s syndrome
significant fetal detha, lymphedema, aortic coarctation and bicuspid aortic valve, short, ovarian dysgenesis and amenorrhea, behavioral probs and learning disabilities.
What gene is responsible for the short stature of turner’s syndrome patients? In what region is it located?
SHOX gene in the pseudoautosomal region
What is the difference between apericentric inversion and and a paracentric inversion?
pericentric inversion occurs across the centromere; paracentric inversion occurs all on the same side of the chromsome
what is an isochromsome?
example of chromsomal duplication when an entire chromosome arm is duplicated, and this duplication replaces the other chromosome arm
exposure to what causes pyrimidine dimers to be formed in DNA?
UV radiation
What are common phenotypes associated with DNA repair disorders?
severe growth deficiencies, premature aging, photosensitivity of skin immunodeficiency and hematological defects, and cancer predisposition
What are the three main ways in which nucleotide bases can be damaged?
oxidation, chemical adducts, and deamination
Describe base excision repair. What is the name of the only genetic defect known to involve base excision repair?
glycosylase removes the damaged base, leaving only the sugar backbone (aka a apurinic/apyrimidinic nucleotide. apurinic/apyrimidinic nucleotide is excised by an AP endonucease, which excises the sugar. then the gap is filled in to pair with the complementary strand, and the strands are ligated. This can happen as either short-patch (single-base damage) or long-patch (2-10 base damage). disorder: hyper-IgM syndrome
What mechanism repairs pyrimidine dimers?
nucleotide excision repair
How does nucleotide excision repair work?
this mechanism repairs pyrimidine dimers. these dimers cause a bulky distortion of the double helix that is detected, leading to the removal of about 25 bases, including the buly bases. The gap is repaired using DNA polymerase delta, proliferating cell nuclear antigen (PCNA), and DNA ligase
What are the two recognition systems for distortions caused by pyrimidine dimers?
global genome pathyway and the transcriptional-coupled pathway
What are some of the clinical manifestations of xeroderma pigmentosum (XP)? How is XP usually inherited?
Most importantly: extreme sunburns after minimal sun exposure, freckling, and high risk of skin cancer. Some eye involvement, especially in the parts of the eye exposed to the sun.
Other possible complications include CNS and neurological complications like microcephaly, progessive hearing loss, and cognitive impairment. usually autosomal recessive
In mismatch repair, what protein recognizes single nucleotide mismatches?
MSH6
In mismatch repair, what protein recognizes small insertions and deletions?
MSH3
What causes Lynch syndrome? What is the clinical manifestation?
Lynch syndrome is caused by defects in the MMR genes (genes for mismatch repair). Patients are usually heterozygous for these defects. Lynch syndrome leads to very high levels of risk for GI, urinary, and endometrial and ovarian cancers. Many of these tumors demonstrate microsatellite instability.
What is microsatellite instability? Where might we observe microsatellite instability?
Microsatellite instability means that the microsatellite loci are highly variable in the length of the alleles at microsatellite loci. This is frequently seen in the tumors of patients with Lynch syndrome as a result of mutations in the genes for mismatch repair.
What enzyme is involved in single-strand break repair? What does this enzyme do?
PARP (poly-ADP ribose polymerase). PARP detects single-stranded breaks and then tags them for repair by sythesis of a poly ADP ribose chain. Inhibition of PARP may help treat cancer.
What are the two types of double strand break repair?
non-homologous end-joining and homologous recombination repair
How does non-homologous end joining work?
It is a way of dealing with a double stranded break. Most of the time, the ends are uneven. First, the protruding end is cleaved (which results in loss of DNA material). Then, rhwew is limited base pairing between the two double stranded DNA strands are filled in, joined by ligation.
What is double strand break repair by homologous recombination?
In homologous recombination repair, a segment of the undamaged chromosome is transferred to over to replace the damaged segment– homologous recombination. One potential consequence is loss of heterozygosity.
What are the four main examples of diseases caused by defects in homologous recombination repair?
Bloom syndrome, Werner syndrome, fanconi anemia, and familial breast and ovarian cancer syndrome
What are clinical manifestations of Bloom’s syndrome, and what is the general cause of bloom’s syndrome?
homologous recombination repair
growth restriction, hypersensitivity to light, infections due to immunodeficiency, chromic pulmonary disease and diabetes mellitus. possible learning disability, male infertility, and early menopause. high risk for cancer. autosomal recessive.