RNA may have preceded DNA - more complex and diverse in functions - BUT DNA is stable

Human Genome and Karyotype Flashcards by Daniel Marino

Genome size
Dna, genes, #chroms
# genes in mito

3.2 billion bps
22,000 genes
23 pairs of chroms
37 genes known

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Chromatid

After DNA is replicated, form a pair of sister chromatids attached by a centromere

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C-value enigma

some single celled organism have larger genome size than humans

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Ploidy

Chrome number does not correlate with genome size/complexity

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Mechs that lead to increased genome comlpexity/size

Duplication of existing sequences (evidenced by multilane families)

Lateral transfer-incorporation of DNA from other species

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RNA vs DNA

RNA may have preceded DNA

more complex and diverse in functions
BUT DNA is stable

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ENCODE Project

Essentially mapped genome for 80 different cell types for exons, histone mods, regions where dna cleaves, binding of many tf factors

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Encode projet conclusions

80% of genome is functional and noncoding regions may be more important than protein coding in determinants of health and disease

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CTCF encriced

insulated-no interactions with enhancers or promoters

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enchancers

open, h3k4me1, h3k28ac, bound tf’s

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Promoters and tf start sites

h3k4me3, bound pol 2/3 and proximal binding tfs

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transcribed regions

h3k36me3, elongationg form of polymerase, polyA+ RNA

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Repressed

H3k27Me3, bound polycomb group proteins

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Functional states of chromatin

cell type specific

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Functional DNA

sequences that display a reproducible biochemical signiture

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Encode on evolutionary genome

a lot of baggage through evolution but doesn’t hurt us enough to be eliminated through evolution

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Variation in genome

Much is of unclear significance-try to find ones that affect phenotype

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Tandem repeats

ancient repeats have diverged in nucleotide over time. recent rrepates have over 90% sequence identity

repeats of genes or blocks of genes

repeats homology make hot spots for recombination
-can cause inversion, duplication or deletion

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% of genome that natural selection operates on

10%

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red green color blindness

Recombination of duplicate genes that are almost same sequence on x chromosome

misalingment in meiosis followed by recombination
may lose a single receptor gene -cant distinguish between red and green

red(long), green(medium_)

males with deleted x have only 1 receptor-cant distinguish

Contiguous gene syndromes

Microdeletion or segmental aneuplidy syndromes

recombination in large repeates deletes a block of dna with multiple genes

Satellite sequences

microsatellites

short repeats

Tandem repeats of sequences a few hundred bp long-around centromeres and telomeres

Repeats of few nucleotides, copy number highly variable-used to identify parents

Called satellites because when dna fractionated-repeats form satellilite seen next to DNA peak

Retrotransposons

mRNA that is reversed transcribed and put somewhere else in genome
-25% of complexity of human genome

insertion into a gene can disrupt function

LINE, SINE, Pseudogenes

LINE-long interspersed nuclear elements-mRNAs encoding reverse transcriptase

SINE-copies of a short cellular RNA
-Alu sequences-most abundant-restriction site for Alu

Copies of cellular mRNAs that ar not transcribed b/c no promoter

When should you consider diagnosis of chromosome abnormality

hysical or menetal dev delayed infertitly, sponaenous abortion, stillbirth prenancy in woen over 35 cancer

G banding

cells incubated with colchicine, cells consense, stain with dye dark-g bands can identify chrome by size, banding pattern, centromere position

cochiicine

binds tubilin, prevents spindle function, arrests cell in metaphase

p vs q arm

p is short, q is long

metacentric, sub metacentric, acro centric, telocentric

middle of chrome somewhat high on chrome very high on chrome at end of chrome-not in humans

g banding resolution

CAN ONLY SEE PROBLEMS OF MUTATIONS THAT ARE SAME AS TEST Detects large changes in chrom structutre lower resolution limit is like 45 genes-cant detect small changes

FISH

Chromatin fixed to slide, probe binds to DNA of complimentary seqeucen Fast when done to interphase cells-lower resolution b/c dna not condensed vs metaphase metaphase need to amplify cell number and use colchicine prentnatal diagnosis NEEDS SPECIFIC PROBE + ONLY DETECT TO POSITION WHERE YOU KNOW PROBE BINDS -cant rule out genetic defects elsewhere

FISH resolution

better in metaphase does not reveal single nucleotide deletion or changes somewhere else in genome useful for detecting monosomes and translocations! -can make more specific with more specific probe (small deletions, but not single base pair deletions) Resolution decreases as number of probes increases

CGH

Comparitive Genome Hybridization Array of oligonucs immobilized at different positions on glass slide (mercury)-completementary to sequenced spaced across genome -compare PCR amplified patient genome with reference Tells deletions, duplications Can plot to see gain/ lose of chromatin Limitation-can detect deletions or duplications but not inversions or translocations

CGH strength/weaknesses

detects very small changes in genome-anywhere Detects only icnreases/cecreases in copy number Cannot detect rearramgents without gain or loss (inversion/translocation)

Human polyploidy

not viable

Euplody vs aneupoidy

normal # vs more or less (trisomy and monosomy) Aneuplodiy lethal for most except X, Y, small autosomes

Trisomy 21/13 designation

47 XY +21 or 47 XX +13

Kleinfelter syndrome designation

47, XXY

Turner syndrome designation

45, X

Translocations (2 types)

Recipricol Non-recpircol

Abnormalites in chroms

translatiocs, inversion, duplications, deletions

Causes of chromosome alterations

dsbreaks in DNA, NHEJ, carcniogenesis, increased by radiation

How to identify + of chromasomes

Number of centromeres and then identify centromere to identify chromosome

Where are most common translocations?

Between afrocentric autosomal chromosomes -conceptions with extrachroms usually die, but those with extra D or G group may survive because small Short p arms of these chrome contain only genes for rRNA (rDNA gene copy number is very large)

Robertsonian translocations and designation

45, xx, 14,21 +rob(14q, 21q) breakpoints occur within centromeres of D and g group chromosomes, with fusion of chromosomes and loss of p arms carrier has normal phenotype no loss of DNA in q arms - short arms often lost, but nonlethal - also have normal chr 14 and 21 from other parent

Results of meiosis in carrier of robertsonian translocation

normal balanced carrier trisomy 14 monosomy 14 monosomy 21 trisomy 21 at meiosis- 1 robertsonian, 1 normal chrome 14, 1 normal chrome 21

isochromasome 21

both arms from 21q viable since diploid for 21q but gametes receive either 1 21 q or no 21 q trisomy 21 (down syndrome or lethal) or monosomy 21 (lethal)

Pericentric inversion

Dna between two breakpoints in the same arm are flipped (only in middle of chromosome but tips are okay)