C3&4 human genome project

Question 1

genome

Answer 1

complete set of chromosomes

Question 2

what does every genetic and physical marker have

Answer 2

a specific locus in genome

Question 3

what was the goal of the human genome project

Answer 3

-determine the seq of the 3 billion chemical base pairs in human DNA
-identify all genes in human DNA to their position on chromosomes
-attempt to predict the function of all genes
-utilise this info for understanding of disease, developing better medicine

Question 4

name given to those who participated in mapping and sequencing process

Answer 4

formal international consortium

Question 5

phase 1 of human genome project

Answer 5

produce high resolution chromosomal maps
-position genetic markers (and genes)
-create libraries of BAC clones for sequencing (physical map)

Question 6

phase 2 of human genome project

Answer 6

sequence each BAC DNA

Question 7

phase 3 of human genome project

Answer 7

assemble all sequences to produce final draft and annotate to identify genes

Question 8

overview of human genome project (7 steps)

Answer 8

1. genomic DNA (2 male, 2 female)
2. BAC library (250,000bp)
3. organised mapped large clone contigs
4. BAC to be sequenced
5. shotgun sequence
6. assembly

Question 9

what maps are combined to order all BACs

Answer 9

genetic and physical

Question 10

what is old sanger sequencing

Answer 10

radiation
4 separate dideoxy reactions
one for each base, very slow, manual reading of results off x-ray fillm

Question 11

new sanger sequencing

Answer 11

like PCR but with fluorescent terminators
-run products on gel
-separated by size
-laser scans bands (ACGT)

Question 12

second phase genome project

Answer 12

-used these advances in sanger DNA sequencing technology and reduction in cost
-computational assembly of all sequences into ‘contig’

Question 13

how to provide one-fold coverage

Answer 13

requires ~3 million separate sequencing reactions producing 1000 bases each

Question 14

draft sequence coverage

Answer 14

4 fold

Question 15

finished sequence coverage

Answer 15

9 fold

Question 16

what is IHGSC

Answer 16

clone by clone approach

Question 17

advantages and disadvantages of IHGSC

Answer 17

-very effective at getting over regions of highly repetitive DNA sequences
-able to retrieve clones later

-slow process
-expensive

Question 18

what is celera

Answer 18

shotgun sequencing
blast genome into small fragments, sequence each one and then use the power of computers to reassemble sequence

Question 19

what did celera have to rely on

Answer 19

public databases of sequence and mapping information in order to assemble the sequence that was generated by this method

Question 20

completion of human genome

Answer 20

-june 2000 white house announced 80% sequenced
-working draft publication made available on web july 2000
-publication of 90%
-completion of 99.99% july 2003

Question 21

how many genes (original 2001 answer)

Answer 21

20,000-25,000 genes
~1.5-5% of the genome

Question 22

genetic variation between humans is visible at the genomic scale

Answer 22

population genetics

Question 23

how many chromosomes were sequenced

Answer 23

10 (5 people)

Question 24

what were the two major types of revelation

Answer 24

single nucleotide polymorphisms (SNPs)
copy number variants (CNVs)

Question 25

what is the international hapmap project

Answer 25

finding the more common SNP varients in the worlds population

Question 26

how many human SNPs in nature in 2005 were reported to HapMap

Answer 26

>1 million

Question 27

what 4 populations of people were studied in HapMap project

Answer 27

270 people nigeria (african) japan and china (asian) utah (northern & western european ancestry)

Question 28

how many gaps were in the original human genome project

Answer 28

8%

Question 29

who published the final results of the HGP

Answer 29

telomere to telomere (T2T) consortium

Question 30

the draft 'T2T-CHM13' annotation totals

Answer 30

63494 genes 233,615 transcripts

Question 31

what increases in complexity as you climb the evolutionary tree

Answer 31

transcript/protein structure

Question 32

6 things learned in HGP

Answer 32

1.how do humans compare to other species 2. humans are evolving 3. fine structure of inheritance 4. human (pre)history 5. way in which our genes control our response to medication 6. disease genes

Question 33

what is comparative genomics and evolution

Answer 33

comparisons with other species is possible to determine evolutionary relatedness and understanding of evolutionary changes in genes/proteins

Question 34

what methods are used to comparative genomics

Answer 34

-sequence alignments across species -genome based phylogenies

Question 35

organism genome comparison (smallest to biggest genes)

Answer 35

E.coli- 4,200 S. cerevisiae (yeast)-6,000 C. elegans (nematode)- 14,000 D. melanogaster (fruit fly)- 14,000 A. thaliana (mustard plant)- 24,000 Mammalian- 20,000-25,000

Question 36

what allows novel genes/proteins during evolution

Answer 36

modular domains

Question 37

many pathways are highly what across species

Answer 37

conserved

Question 38

what is TBC1D3

Answer 38

only found in humans regulates growth factors and role in RAS-mediated cancers

Question 39

examples of selective expansion in protein families and domains

Answer 39

-immune function -intercellular signalling -metabolic function -olfaction -haemostasis -apoptosis -neural function -translation

Question 40

how many genes with human specific features vs how many entirely human specific genes

Answer 40

850 50+

Question 41

what kinds of genes show evidence for fast/recent evolution in humans

Answer 41

-pathogen response -cell cycle/DNA metabolism -protein metabolism -reproduction -neuronal activity -skin pigmentation

Question 42

2 gene selections showing evidence for fast/recent human evolution

Answer 42

HBB gene selection haemoglobin B (anaemias) LCT gene selection lactase gene variants selected for in early human groups which used milk in diet

Question 43

how do most HIV strains enter cells

Answer 43

using CCR5 as main co-receptors (with CD4)

Question 44

how do some people have natural resistance to HIV infection

Answer 44

homozygous for ∆ 32 mutation on CCR5 gene

Question 45

what is the paradox of CCR5 ∆32 variant prevalence

Answer 45

distribution requires millennia but HIV only around since 1970/80s

Question 46

possible explanation for paradox of CCR5 ∆32 variant prevalence

Answer 46

∆ 32 may have been protected (been selected for in) ancestral populations against earlier HIV like epidemics or even small pox NOT bubonic plague/yersinia pestis ass was once thought

Question 47

what is FOXP2

Answer 47

gene involved in human speech and language disorders potentially critically involved in human specifiic development of language 2 aa changes between chimps and humans/neanderthals/denisovans

Question 48

example of human specific loss of sequences

Answer 48

olfactory genes

Question 49

how were LD blocks discovered

Answer 49

through the study of common variants

Question 50

term given to haploid genotype

Answer 50

haplotype

Question 51

how are haplotypes formed

Answer 51

formed by a collection of linked marker alleles on one chr that are inherited together

Question 52

over short distances how do haplotypes remain intact

Answer 52

not disrupted by meiotic reccombination

Question 53

what are the very short distances of haplotypes that remain intact called

Answer 53

linkage disequilibrium blocks [LD blocks] unit of inheritance

Question 54

where does chiasma formation in meiosis happen

Answer 54

hotspots an LD block is the same in between

Question 55

what populations show highest levels of genetic polymorphisms

Answer 55

african

Question 56

every other continent has less genetic variation than africa but some from what

Answer 56

archaic humans

Question 57

what is mediated by genetic differences in terms of drug treatment

Answer 57

individual variation

Question 58

what factors are under genetic control in pharmacogenetics

Answer 58

-inactivation/activation by oxidative pathways (cytochrome P450s) -conjugation for excretion through the kidney (GST) -target sensitivity -toxicity=side effects -disease mutation type

Question 59

what is an advent of personalised/stratified medicine

Answer 59

identifying patients who will respond well to drug treatment

Question 60

pharmacogenomics knowledge applied with example

Answer 60

screening patients for CYP2C9 and VKORC1 gene varients identifies those who should start on a low dose of warfarin to avoid risk of internal bleeding

Question 61

what variants affect antidepressant escitalopram serum conc and treatment success

Answer 61

CYP2C19

Question 62

PegIFN-a-2b or PegIFN-a-2a combined with RBV for what treatment

Answer 62

hep c

Question 63

in terms of CF what is the most common mutation in european pops and what is the result

Answer 63

DF508 no protein produced

Question 64

in terms of CF what percentage of mutations just damage the function of the protein

Answer 64

5%

Question 65

in terms of CF what drug is used to restore function

Answer 65

ivacaftor

Question 66

8.5 in 100,000 users of flucloxacillin have what reaction

Answer 66

serious liver reaction called drug induced liver injury (DILI)

Question 67

what has been associated with DILI risk from flucolaxacillin

Answer 67

an SNP marker rs2395029[G]

Question 68

what can be said about the SNP marker associated with flucolaxacillin (linkage)

Answer 68

marker in complete linkage disequilibrium [LD] HLA*7501 immune cell surface protein

Question 69

basic research practical uses of human genome project

Answer 69

all genes known forever vast and integrated info set based on genome publicly available

Question 70

medical advances since human genome project

Answer 70

-pharmacogenomics; right drug for right people -genome wide genetic studies offer best hope of cracking complex genetic disorders -diagnostic tests