LEC43: Intro to Genomics Flashcards
what does every human cell contain?
complete genetic code
when are chromosomes visualizable?
during mitosis, when chromosomes condense
what was first genome screen technology?
karyotyping by G-banding
what was reference human genome, its use?
traditional sequencing method: took DNA from individual, arranged into pieces of chromosomes, chopped up, individually sequenced, stitched back together, compared to reference human genome
= sanger sequencing
costly and slow, not method anymore
what did human genome project do?
sequence entirety of human genome
took 10 yrs, $1 billion
info acquired allowed cataloging of complete set of human genes
what did human genome proj find?
complete set of human genes = similar to number observed in other model organisms like mouse, watercress plant, roundworm
explanation: complexity in mammals due to alternative splicing, permitting increased number of potential proteins
how much of our DNA is protein coding genes?
1.5%
what is difference between number of genes, gene density, in humans vs plants?
genome size is similar
but gene number is much greater in humans
thus human’s avg gene density is much lower; only 1.5% of our DNA encodes proteins
due to alternative splicing
what is result of alternative splicing?
from 1 single gene, exons’ arrangement can be different, get different resulting proteins!
only 1.5% of our DNA is protein coding, though
how much of non-gene DNA is conserved?
2-5% of non-gene DNA is conserved through evolution
if a piece of DNA is conserved, what does that suggest?
that it’s important
basis for idea that there’s functionality among non-gene portions of our DNA that’ve been conserved through ages/across animals
suggests these regions have important regulatory role in genome function
HOXD gene cluster function?
basic body patterning control
example of conserved region of essential proteins that regulate genome function
how much of our genome is repeat elements?
what are they relics of?
50%
relics of retrovirsues and ‘genomic parasites’ that invaded our DNA in evolutionary history, i.e. HIV - ‘junk DNA’
what causes finger webbing?
mutation in hoxD gene cluster, as HoxD genes encode for basic body patterning
segmental duplications?
blocks of DNA 1-500 kb in length that occur at multiple sites in the genome, share a high level of sequence identity
~5% of our DNA
can be intrachromosomal (same chromsome) duplications or interchromosomal (between chromosomes)
what role do segmental duplications play in genetic disease?
these large highly idneitical repeats often flank certain regions of the genome that are thus prone to misalignment during meiosis, leading to improper recombination
if any repeats are dosage sensitive, results in genomic deletions and/or duplications that are associated w/ a particular genetic disease
examples of recurrent genomic disorders?
velocardiofacial syndrome
angelman/prader-willi syndrome
charcot-marie tooth disease
x-linked hemophilia
all caused by mechanism of recombination between large high-identity repeats
recurrent deletion on chromosome 15 causes what/example of what?
causes intellectual disability, dysmorphisms, epilepsy
deletion = most common known genetic cause of epilepsy, present in ~1% of epilepsy patients
example of recurrent genomic disorder caused by aberrant recombination between large high-identity repeats
how many bases of difference exist between 2 individuals?
avg ~6 million bases, ~0.1% of genome
means 99.9% shared DNA among humans
what are the types of variation in the human genome? from smallest to largest
1) single base-pair changes - point mutatoins/SNVs/SNPs
2) small insertions/deletions & microsatellites
3) mobile elements - retroelement insertions (300 bp - 10kb in size)
4) large-scale genomic variation (>1 kb) - deletions, duplications
5) chromosomal variation - translocatoins, inversions, trisomy
most common type of genetic variant?
SNVs, single nucleotide variants or polymorphism or point mutation
occurs 1x every 1,000 bp = 3-5 million SNVs in individual genome
where do SNVs usually occur?
most in non-coding regions - may have regulatory effects, but not well understood
however, 10,000 per genome (0.3%) are in coding regions, & cause changes in protein sequence
what do SNPs within coding regions cause?
sometimes, no change, since a.as are reduntant
sometimes, changes amino acid, different protein results
what do SNPs outside of coding regions cause?
how much of SNPs are outside of genes?
can influence disease by altering gene regulation
i. e. if change a ntd within txn factor binding site code, txn factor may not recognize, may not bind to DNA, no activation occurs, gene may be OFF when should be ON
99. 7% of SNPs are outside of genes
