Lecture 15

Question 1

genome

Answer 1

the complete set of genetic material present in a cell or organism

Question 2

genomics

Answer 2

the cloning and molecular characterization of entire genomes

Question 3

a haplotype

Answer 3

The specific set of SNPs and other genetic variants observed on a single chromosome or part of a chromosome

Question 4

linkage disequilibrium

Answer 4

The nonrandom association between genetic variants within a haplotype

Question 5

tag-SNPs

Answer 5

The few SNPs used to identify a haplotype

Question 6

Genome-wide association studies use

Answer 6

numerous SNPs scattered across the genome to find genes of interest

Question 7

annotated (gene) which means

Answer 7

linking its sequence information to other information about its function and expression, the protein it encodes, and similar genes in other species.

Question 8

Metagenomics is an emerging field in which

Answer 8

the genome sequences of an entire group of organisms that inhabit a common environment are sampled and determined.(eDNA)

Question 9

Synthetic biology seeks to

Answer 9

design organisms that might provide useful functions

Question 10

Functional genomics

Answer 10

characterizes what sequences do—their function

Question 12

Genome content consist of

Answer 12

much more than just protein-coding genes

Intergenic sequences. → “non-coding” DNA

Repetitive sequences → short and long sequences that repeat in tandem or are interspersed throughout the genome

Question 13

prokaryotic and eukaryotic genomes differ drastically in

Answer 13

size & organization

prokaryote - attached to cytosol (no organells, DNA not in nucleus)

eukaryote - genome in distinct chromosomes - tightly bound to proteins

Question 14

Anatomy of a prokaryotic genome

Answer 14

1) single, circular chromosome

2) Single origin of replication (req. for DNA rep. machenerary)

3) Genomes are compact
→. ~1-10 million bases (Mb)

4) Most content is genic
→ Minimal intergenic DNA (non- coding)
→ few repetitive sequences
→ No introns

5) Genome size is directly related to gene content
→ larger genomes encode more proteins

Question 15

regulatory consequences of organization of prokaryotic genome

Answer 15

Genes in biochemical or signaling pathways often clustered and controlled as operons

Chromosome not sequestered in nucleus

Chromosome not bound by histone proteins
→ No chromatin

Question 16

Eukaryotic genomes

Answer 16

1) Genomes divided into multiple linear chromosomes, with telomeres & centromeres

2) DNA complexed with histone proteins (=chromatin) in a nucleus

3) Genome size tends to be much larger, and varies widely, even within a taxonomic group
→ Genes interrupted by introns
→ Copious intergenic DNA
→ Copious repetitive DNA

4) Genomes don’t tend to be compact

5) With rare exceptions, genes not clustered into operons

6) Many genes (most human genes) are interrupted by introns; genes are far apart

Question 17

C-value is the

Answer 17

DNA content per haploid cell
→ think of this as genome size (how many bp)

Question 18

G-value is the

Answer 18

protein-coding gene number
(amount of DNA seq corresponds to coding protein)

Question 19

G-value paradox

Answer 19

Gene number does not fully correlate with organismal complexity

Question 20

G-value paradox explained by

Answer 20

(1) alternative splicing
(2) expansion/contraction

Question 21

alternative splicing explanation for G-value paradox

Answer 21

Multiple exons from one gene can be spliced in different ways (=alternative splicing) to form distinct mRNAs and proteins

No. of proteins&raquo_space; no. of protein coding genes

Explains smaller-than-expected gene count in multicellular spp.

Question 22

expansion/contraction explanation for G-value paradox

Answer 22

Gene expansion & contraction is frequent, even among closely related spp.

gene duplication
family duplication
entire genome duplicated

Question 23

C-value paradox

Answer 23

Genome size doesn’t fully correlate with organismal complexity

Question 24

C-value paradox explanation

Answer 24

expansion of non-genic DNA, largely repetitive DNA

> 85% of human genome is repetitive DNA → caused by interspersed transposable elements → non-autonomous, non-coding transposable elements

Question 25

Assembly of eukaryotic genomes is

Answer 25

very challenging Human genome is 3,200 Mb (million bases; =3.2 Gb) with large amounts of repetitive DNA. Technology not up to the task: Sanger sequencing

Question 26

Draft human genome reference assembly

Answer 26

Sequencing is only the beginning, resulting in multiple millions of “reads” Assembly → sequencing reads must be put in order on chromosomes (we are skipping this aspect) Draft assembly → unfinished, with lots of “gaps” Reference assembly → the assembly (usually a working model) is used as a framework to guide interpretation of individual genome variation and functional genome analysis

Question 27

HGP brought about

Answer 27

radical technological changes in genetics and radical conceptual changes in genetics

Question 28

technological changes in genetics brought about by HGP

Answer 28

High throughput, massively parallel, genome-wide data collection and functional assays Sequencing efficiencies → 1 human genome: from 10 years and 2.7 billion (1990-2003) to 1 day and <$999 in 2019 Concomitant strides in computing power and analysis software

Question 29

conceptual changes in genetics brought about by HGP

Answer 29

Humans are more variable than we thought Humans have far fewer protein-coding genes than we thought… …yet, most of the genome is transcribed → a lot of RNA not turned into proteins Cells are full of noncoding RNAs

Question 30

Initial predictions before the Human Genome Project were ____ Current estimate is ___

Answer 30

~200,000 ~20,000 or less caveat: we need to reconsider how a “gene” is defined, as we will see later in the course

Question 31

Functional Genomics

Answer 31

how to go from DNA to what do

Question 32

Genome controls phenotype through

Answer 32

transcription

Question 33

We expect that functional elements in the genome should be

Answer 33

1) transcribedor 2) bind proteins that regulate transcription

Question 34

Bioinformatics involves ___ which can ____

Answer 34

using computer technology to collect, store, analyze and disseminate biological data and information can increase our understanding of health and disease and, in certain cases, as part of medical care.

Question 35

Homologous genes

Answer 35

Genes that share a common evolutionary origin. Likely to have conserved sequence and function.

Question 36

Paralogs

Answer 36

Homologous genes in the same species. e.g. alpha and beta hemoglobin in humans.

Question 37

Orthologs

Answer 37

Homologous genes in different species. e.g. mouse and human alpha hemoglobin

Question 38

Predict function from sequence

Answer 38

how closely related to other genome (ex. SARSr-CoV)

Question 39

Comparative genomics

Answer 39

field of genomics that studies similarities and differences in gene content, function, and organization among genomes of different organisms

Question 40

Transcriptome

Answer 40

All RNA molecules transcribed from a genome

Question 41

Transcriptomics

Answer 41

Techniques used to identify and quantify the transcriptome.

Question 42

protein domains

Answer 42

Complex proteins often contain regions, called that have specific shapes or functions (ex. zinc finger)

Question 43

RNA-seq

Answer 43

Transcriptomics identifies all transcribed elements → extract all cellular RNA → transcribe → cDNA → chop up and add adapters → sequence Relies on next generation sequencing and bioinformatics

Question 44

Microarrays

Answer 44

Transcriptomics Can be used to determine relative levels of mRNA (i.e. expression levels) for 1000’s of genes. Employ an array of complementary probes that are complementary to mRNA sequences.

Question 45

Proteome

Answer 45

All proteins encoded in a genome.

Question 46

Proteomics

Answer 46

Techniques used to identify and quantify the proteome.

Question 47

Mass spec

Answer 47

Proteomics is a high throughput method to identify proteins in a cell → digest proteins into peptides → separating fragments by mass-to-charge ratio → match peak profiles to a database of known proteins

Question 48

ChIP-seq

Answer 48

(Chromatin ImmunoPrecipitation) Proteomics (affinity capture) identifies DNA bound by known DNA-binding proteins → e.g., transcription factors (TFs), RNA pol antibodies bind to specific protein → take genomic DNA → mix with antibody → bind to protein (that is bound to DNA) → can pull complex out of solution and seq DNA bound by that protein Requires specific antibodies → need to know what protein looking for (and have antibody for it) high throughput sequencing

Question 49

two-dimensional polyacrylamide gel electrophoresis

Answer 49

(2D-PAGE), proteomics in which the proteins are separated in one dimension by charge, separated in a second dimension by mass, and then stained

Question 50

Protein Microarrays Employ ___ Can be use to ____

Answer 50

Proteomics Employ an array of proteins immobilized on a solid support. to identify protein-protein interactions or measure expression of proteins within cells (using immobilized antibodies).

Question 51

Modifications of affinity capture and other techniques can be used to ____ termed the_____

Answer 51

determine the complete set of protein interactions in a cell, interactome.

Question 52

Genome-wide mutagenesis screens

Answer 52

can be used to search for all genes affecting a particular function or trait. two methods—random inducement of mutations on a genome-wide basis and mapping with molecular markers—are coupled and automated

Question 53

segmental duplications,

Answer 53

duplicated regions greater than 1000 bp that are almost identical in sequence. Many eukaryotic genomes, especially those of multicellular organisms, are filled with

Question 54

multigene family is a

Answer 54

group of evolutionarily related genes that arose through repeated duplication and evolution of an ancestral gene.

Question 55

gene deserts

Answer 55

(genetically engineered mice that were) missing large chromosomal regions with no protein-encoding genes

Question 56

collinearity

Answer 56

many genes are present in the same order in related genomes

Question 57

pangenome

Answer 57

the entire set of genes possessed by all members of a particular species.

Question 58

single-nucleotide polymorphism (SNP)

Answer 58

A site in the genome where individual members of a species differ in a single base pair