Ch 8 - Genomics

Exam 1

Genomics

DNA sequencing (predict genes, proteins, protein functions, pathways)

Transcriptomics

RNA sequencing

Proteomics

analysis of protein/complex purification and mass spec

Metabolomics

analysis of metabolites (mass spec and nmr)

size of human map unit

1,000,000 bp

High-resolution recombination mapping

used to find the location of a gene/mutation on a chromosome by analyzing recombinant events (crossing over)

Cytogenetics

microscopic study of chromosomes

FISH (fluorescent in-situ hybrid)

• used to detect specific DNA or RNA sequences using fluorescence

• fluorescent probe is short, single-stranded complementary sequence to target

Bacterial Artificial Chromosomes (BAC)

constructed DNA clones for large DNA fragment ~300kb

contigs

long contiguous stretches of chromosome DNA

primer walking

• method to fill in unknown gaps in DNA sequences

• primer from known region is used to obtain the new sequence

• new primer created from that in the unknown region overlapping with previous sequence

• process repeated

Whole-genome shotgun sequencing (WGS)

• used to determine the entire genome sequence of an organism

• randomly fragment the DNA, sequence the overlapping fragments, put it all together

• only works for small genomes

Size of human genome

3 billion bp

Haplotype

Set of DNA inherited together because of their proximity on the same chromosome

Odds of recombination

=1% recombination * # of generations * fragment length consider / 1,000,000 bp per map unit for humans

Homolog

genes related by descent from common ancestor

Ortholog

• gene from different species that evolved from common ancestor by speciation

• retain same function

Paralog

• genes related by duplication within genome

• may evolve new functions

C-value paradox

lack of correlation between genome size and developmental/metabolic/behavioral complexity

Introns

• noncoding regions of DNA that are removed

• 25% of genome

microRNA and long noncoding RNA

regulates gene expression at different levels

Satellite (repetitive) noncoding RNAs

play a role in establishing condensed heterochromatin at centromeres and telomeres

short tandem repeat (STR)

short sequences (2-6 bp) repeated consecutively

transposable elements (TE)

• "jumping genes”

• DNA sequences that can move from one location to another in the genome

• moving locations can cause mutations

synteny

conserved gene content among organisms that recently diverged

ex) last common ancestor between human and mouse was 90 million years ago yet 85% sequence synteny

Robertsonian translocation

• long arm of two chromosomes fuse together

• human chrom 2 is result of fusion of ape chrom 12 and 13

Neandertal genome is ___% identical to modern humans

All modern humans are ___% identical

Chimpanzees are ___% identical to modern humans

99.7%

99.9%

99.0%

Positive selection in Neanderthal genes

• genes affecting keratin function in skin/hair

• genes involved in immune system function

Negative selection in Neanderthal genes

some genes contribute to diseases (Type II diabetes)

Denisovans

• extinct relative of Neanderthals

• hypoxia gene caused high altitude adaptation in Tibetans

TKTL1

• gene that is active in frontal brain cortex in humans

• involved in glucose metabolism and cell cycle regulation

• less neurons formed in Neanderthals TKTL1 than modern human

Fibroblasts

• type of cell contributing to formation of new connective tissue

• induces pluripotent stem cells

continued lactase production in adults

• mostly in Africa, Middle East, Europe

• due to domestication of cattle, camels

Different skin colors

• light skin allows vitamin D production under low light

• Dark skin protects against skin cancer in high light

Glucose 6P dehydrogenase

• high levels defend against free radical damage

• low levels provide partial protection against malaria

alpha-amylase

• high numbers in populations with high starch diets

• humans have 1-9 copies of the gene

linear chromosome requirements

telomeres, centromeres, origins of replication

4.5 million base pairs

bacteria genome size

4,400 genes

number of genes in bacteria

21,000 genes

number of genes in a worm (C. elegans)

3 billion base pairs

human genome size

20,000 genes

number of genes in human