Genome Organization

Question 1

How is the Human Genome a record of human evolutionary history?

Answer 1

It reflects results of different selection pressures that have occurred over time and shaped our genome (and shaped us)
Genes and genomic features that have been adaptive have been retained
Genotype + environment = phenotype

Question 2

How is genomic variation the fuel of evolution?

Answer 2

Random variation in a highly ordered structure = almost always deleterious consequences
Genetic disease is the price we pay as a species to continue to have a genome that can evolve, i.e., that can adapt to new and changing environments

Question 3

_____ new mutations occur in each individual.

Answer 3

~30

Question 4

Average of 1 SNP every _______ bp between any two randomly chosen human genomes

Answer 4

1000. 99% identical 3,000,000 differences!

Question 5

Give examples of gene-rich and gene-poor chromosomes

Answer 5

Rich = 19
Poor = 13, 18, 21

Question 6

G-C rich regions comprise ___% of the genome, while A-T rich comprise ___%. Clustering of these regions is the basis for ____________.

Answer 6

38%; 54%; chromosomal banding patterns (cytogenetics, karyotype analysis)

Question 7

Most of the genome is stable, but some areas are unstable, which are associated with ___________

Answer 7

disease: SMA (Chr 5q13); DiGeorge syndrome (Chr 22q); 12 diseases (1q21)

Question 8

_________ chromatin is more relaxed, and _________ is more condensed.

Answer 8

Euchromatic = TRUEchromatic = relaxed
Heterochromatin = compact/condensed

Question 9

Most of the non-sequenced regions of the genome are in ___________, but some are in the __________ region because _____________.

Answer 9

heterochromatic region, but some are in the euchromatic region because of large segmental duplication (10kb - 1Mb)

Question 10

_______% is translated (protein-coding)

Answer 10

1.5%

Question 11

______% codes for genes (introns + exons + flanking sequences)

Answer 11

20-25

Question 12

_________________ are the basis for cytochromatic banding.

Answer 12

tandem repeats, aka “satellite DNA.” Some are found as part of human-specific heterochromatic regions on the long arms of Chr 1, 9, 16, Y (hotspots for evo changes)

Question 13

__________________ are found near centromeric regions.

Answer 13

alpha-satellite repeats (171bp unit)

Question 14

Describe 2 types of Dispersed repetitive elements

Answer 14

Alu family (e.g. SINEs) ~300 bp related members, 500,000 copies in genome
L1 family (e.g.LINEs) ~6 kb related members, 100,000 copies in genome
Retrotransposition may cause insertional inactivation of genes
Repeats may facilitate aberrant recombination events between different copies of dispersed repeats leading to diseases
Non-allelic homologous recombination (NAHR)

Question 15

What are the types of human DNA variation?

Answer 15

Indels: minisatellites (tandemly repeated blocks of DNA, VNTRs) and microsatellites (2-4nt repeats, 50,000 per genome, STRP)
SNPs: 1/1000 bp, detectable via PCR
CNV: vary from 200 - 2M bp

Question 16

What is a gene family?

Answer 16

Composed of genes with high sequence similarity (e.g. >85-90%) that may carry out similar but distinct functions
Arise through gene duplication, a major mechanism underlying evolutionary change.
When a gene duplicates it frees up one copy to vary while the other copy continues to carry out a critical function

Question 17

Some CNV regions involved in rapid & recent evolutionary change, such as

Answer 17

• enriched for human specific gene duplications
• enriched for genome sequence gaps
• enriched for recurrent human diseases
• 1q21.1; 9p13.3-9q21.12, 5q13.3

Question 18

CNV loci cover __% of the genome and are implicated in ___________.

Answer 18

12%; increasingly larger number of diseases