Genome organization

Question 1

number of human chromosome pairs

Answer 1

23; 22 autosomal, 1 pair sex

Question 2

base pairs in haploid genome

Answer 2

3X10^9

Question 3

what percent of the genome codes proteins

Answer 3

<1.5%, only about 5% contains regulatory information

Question 4

point of attachment for cell microtubules for cell division

Answer 4

centromere

Question 5

centromeric DNA sequence

Answer 5

alpha satellite family, and appx 171-bp unit critical for the attachment of microtubules of the spindle apparatus

Question 6

the Alu family and the LINE (L1) family

Answer 6

two salient examples of repetitive DNA sequences that have implications in disease

Question 7

define: single nucleotide polymorphism

Answer 7

occurs when a single nucleotide differs in a sequence that ultimately accounts for two alleles.
average of 1 SNP for every 1000 bp

Question 8

the three gene poor chromosomes

Answer 8

13, 18, 21; these are the only ones that can have viable life

Question 9

unstable dynamic regions

Answer 9

common mutations, so common sites for disease

eg. SMA (Chr 5q13); DiGeorge syndrome (Chr 22q); 12 diseases (1q21)

Question 10

the dynamic nature of the human genome

Answer 10

~30 new mutations for each new individual, Shuffling of regions at each meiosis due to recombination
Can produce somatic DNA changes as well as germ-line DNA changes

Question 11

Gene-rich regions/chromosomes

Answer 11

chromosome 19

Question 12

the non-random distribution) of GC-rich (38% of genome) and AT-rich (54%) regions is called:

Answer 12

clustering. this is the basis for chromosomal banding patterns (cytogenetics, karyotype analysis)

Question 13

euchromatic regions

Answer 13

more relaxed

Question 14

heterochromatic regions

Answer 14

more condensed; repeat rich

Question 15

percentage of DNA represented by genes (exons, introns, flanking sequences involved in regulating gene expression)

Answer 15

20-25%

Question 16

percentage of DNA that is “single copy” sequences

Answer 16

50%

Question 17

percentage of DNA that are classes of “repetitive DNA”

Answer 17

40-50%

Question 18

how big is the dystrophin gene (on the X chromosome)

Answer 18

big, over 2 million base pairs, less than 1% are coding exons. mutations lead to Duchenne muscular dystrophy

Question 19

very large arrays of tandemly repeating, non coding DNA

Answer 19

satellite DNA; the main component of functional centromeres (alpha satellite), and heterochromatin, or even in human-specific heterochromatic regions on the long arms of Chr 1, 9, 16 and Y (hotspots for human-specific evolutionary changes)

Question 20

of SINEs: Short Interspersed repetitive Elements

Answer 20

Alu family, - ~300 bp related members

- 500,000 copies in genome

Question 21

of LINES: Long Interspersed repetitive Elements

Answer 21

L1 family,- ~6 kb related members

- 100,000 copies in genome

Question 22

Repeats may facilitate aberrant ______________ between different copies of dispersed repeats leading to diseases

Answer 22

Non-allelic homologous recombination (NAHR)

Question 23

Retrotransposition may cause __________ inactivation of genes

Answer 23

insertional

Question 24

giemsa banding

Answer 24

A,T rich regions (gene poor) take up the dark stain,

Question 25

Insertion-deletion polymorphisms (indels):

Answer 25

Minisatellites and microsatellites

Question 26

Minisatellites

Answer 26

tandemly repeated 10-100 bp blocks of DNA VNTR (variable number of tandem repeats) dozens in the genome

Question 27

Microsatellites

Answer 27

-di-, tri-, tetra-nucleotide repeats ->5 x 104 per genome STRPs (Short Tandem Repeat Polymorphisms) thousands in the genome

Question 28

Copy number variations (CNVs)

Answer 28

- variation in segments of genome from 200 bp – 2 Mb - can range from one additional copy to many - array comparative genomic hybridization (array CGH) - implicated in lots of diseases

Question 29

typical gene

Answer 29

intron containing

Question 30

retroposed gene

Answer 30

intronless

Question 31

evolutionary hotspots on chr 1, 9, 16, Y

Answer 31

a particular pentanucleotide sequence on human specific heterochromatic regions

Question 32

SNPs can easily be detected by

Answer 32

PCR

Question 33

describe gene families

Answer 33

Gene family is composed of genes with high sequence similarity (e.g. >85-90%) that may carry out similar but distinct functions

Question 34

how do gene families arise?

Answer 34

through gene duplication, thus is a major mechanism for evolutionary change

Question 35

beta globin # of exons? mutations can cause?

Answer 35

3 exons; hemoglobin deficiencies

Question 36

BRCA1 # of exons? mutations can cause?

Answer 36

24 exons; inherited breast and ovarian cancer

Question 37

MYH7 # of exons? mutations can cause

Answer 37

40 exons; inhereted cardiomyopathy

Question 38

CNV loci may cover ________% of the genome

Answer 38

12

Question 39

examples of CNV implicated in human disease

Answer 39

1q21.1; 9p13.3-9q21.12, 5q13.3

Question 40

CNV example of a Link between evolutionarily adaptive copy number increases and increase in human disease

Answer 40

1q21.1 macrocephaly, autism

Question 41

1q21.1 deletions

Answer 41

microcephaly, schizophrenia

Question 42

genome wide association studies

Answer 42

focuses on SNPs

Question 43

nextgen sequencing limitations

Answer 43

relies on short read sequences; Complex, highly duplicated regions are typically unexamined. Such regions are implicated in numerous diseases, e.g. 1q21

Question 44

explain "missing heritability"

Answer 44

Many large-scale studies implicate loci (e.g. SNPs) that account for only a small fraction of the expected genetic contribution. answer may lie in unexamined DNA