Mtc: Jan 3 Part 4-Human Genome Evolution And Genomic Disorders

Front 1

During DNA replication of genetic regions with a high density of repetitive sequences, "______ _____" of the two strands of the double helix may occur with the formation of a single-stranded hairpin structure.

Back 1

Backward Slippage

Front 2

What is the result of a backward slippage?

Back 2

-One of the two DNA molecules synthesized will have a longer tract of repeats=EXPANDED

Front 3

What results from forward slippage?

Back 3

Contraction of the tandem repeat region

Front 4

Name The Types of Duplications

Back 4

-Tandem gene duplication by unequal crossing over
-Transposition-based gene duplication
-Sequence duplication due to replicative slippage
-Chromosomal duplication: reproductive consequence of translocations and inversions
->Segmental duplication
-Whole genome duplication: polyploidy

Front 5

What may occur after duplications?

Back 5

Mutations

Front 6

What occurs after a mutation?

Back 6

-Variance cause selection and divergence: adaptation

Front 7

What occurs after selection and divergence?

Back 7

Non-selection and divergence: polymorphism

Front 8

Give the time line of mutation to divergence.

Back 8

Duplication-->Mutation-->Selection and divergence (adaptation)-->Non-selection and divergence (polymorphism)

Front 9

What property of phenotypes must be present for mutations?

Back 9

Must be expressed

Front 10

____ _____ and ___ ____ that have been "finely tined" by natural selection generally seems to be quite precisely organized.

Back 10

Coding Sequence and regularatory elements

Front 11

What is a way in which pseudogenes formed?

Back 11

Mutations result in an inactivation of a duplicated gene copy

Front 12

What does the rate of sequence divergence between two genes depend on?

Back 12

Selective pressure applied

Front 13

What are responsible for the abundance of paralogs in our genome?

Back 13

Repeated cycles of gene duplication, mutation, selection and divergence

Front 14

When may speciation occur?

Back 14

When the divergence of the entire collection of genes between two genomes results in reproductive identities=speciation occurs

Front 15

True or False: Duplicated sequence has no selective advantage.

Back 15

False: It has selective advantage

Front 16

What is a selective advantage when sequences are duplicated?

Back 16

-Conservation of sequence

Front 17

Paralogs and orthologs that have taken on new functions are said to have _____ ______.

Back 17

Functionally diverged

Front 18

How may have clustered or dispersed gene families arise during evolution?

Back 18

Duplication of genes and gene regions may occur on the same or different chromosomes

Front 19

Is there a selective pressure for noncoding sequences?

Back 19

No

Front 20

What are non-coding sequences evolve?

Back 20

"Selfish DNA"
-Robustness of how these sequences can duplicated themselves

Front 21

List components of the evolution of non-coding sequence.

Back 21

-Selection-neutral for organism
-Positive selection based on “replicative robustness” of the sequence (“Selfish DNA”)
-Negative selection due to replicative burden on the genome
-Example: transposable elements

Front 22

Describe transposition-based mutations.

Back 22

Insertional mutagenesis
Exon shuffling
Weak poly A signal of L1
Transcriptional read-through
Reverse transcription
Re-integration
Relocation of exon

Front 23

What increases the likelihood of genetic rearrangement through homologous recombination?

Back 23

Duplicated retrotransposons throughout the genome

Front 24

What may be a reason for Williams syndrome and DiGeorge/velocardiofacial syndrome?

Back 24

-Deletions that may be mediated by intra-chromosomal recombination events

Front 25

What region on a chromosome is deleted in Williams syndrome?

Back 25

Chromosome 7

Front 26

What region on a chromosome is deleted in DiGeorge/velocardiofacial syndrome?

Back 26

Chromosome 22

Front 27

What may occur due to an non-allelic homologous recombination?

Back 27

Homologous recombination between the repeats will result in a daughter chromosome that have gained or lost a copy of the specific gene.

Front 28

Recombination

Back 28

A process in which DNA molecules are cleaved and the fragments are rejoined such that new sequence combinations are formed

Front 29

Homologous Recombination

Back 29

recombination between DNA molecules that have sequence homology

Front 30

2 Main Natural Functions of Homologous Recombination

Back 30

1. Homologous Recombination Repair
2. Meiotic Recombination (aka General Recombination)

Front 31

Homologous Recombination Repair

Back 31

-Double-stranded damage to a chromosome is repaired by the transfer of a strand from the homologous (and undamaged) chromosome through the formation of so-called Holliday structures

Front 32

Meiotic Recombination (Type of Homologous Recombination)

Back 32

-During meiosis, the exchange of chromosomal segments between maternal and paternal homologs of the same chromosome (crossing-over)

Front 33

2 Broad Classes of Non-homolgous recombination events

Back 33

1. End-to-End Rejoining
2. Site-specific recombination

Front 34

End-to-End Rejoining (Type of Non-homologous Recombination)

Back 34

-End-to-End rejoining of DNA fragments with broken ends through the formation of a "synapse" where a complex including a DNA-dependent protein kinase (DNA-PK) carries out the reactions

Front 35

What carries out the reactions in an End-to-End Rejoining of non-homologous chromosomes?

Back 35

-DNA-dependent protein kinase (DNA-PK)

Front 36

Site-Specific Recombination (Type of Non-Homologous Recombination)

Back 36

-Mobile genetic elements are moved from one genomic location to another
-Can alter order or add new information into a gene region

Front 37

Where do breakage reactions usually occur?

Back 37

-At the ends of the embedded DNA sequence

Front 38

Transpositional Site-specific recombination (aka Transposition)

Back 38

-the intervening segment between breakage points is released, only to reattach at one of many non-homologous sites in the genome

Front 39

Mobile genetic elements that participate in transpositions are called ______ ____, or simply _______.

Back 39

-Transposable elements
-Transposons

Front 40

What enzymes catalyze the breakage reactions and subsequent reattachments of tranposons?

Back 40

-Trasposonases

Front 41

Transposable elements that contain protein-coding sequences for key enzymes for carrying out the transposition are described as _______.

Back 41

Autonomous

Front 42

Mobile elements that remain as a DNA molecule throughout the transposition are called ___ ___ ____.

Back 42

DNA-only transposon

Front 43

Retrotransposons (aka retroposons)

Back 43

-Produces an RNA intermediate, which is then reverse-transcribed into cDNA by a reverse transcriptase before reattachment

Front 44

Two types of Retrotransposons

Back 44

1. Retrovirus-like retrotransposons (LTR transposons)
2. Non-Retroviral Retrotransposons

Front 45

Retrovirus-like retrotransposons

Back 45

-No actual retroviral particle is involved or created
-Use the same mechanism as retroviruses to create DNA molecules that integrate into other chromosomal regions

Front 46

What are retrovirus-like retrotransposons characterized by?

Back 46

-Long terminal repeats (LTR) on both sides of a central protein-coding region
-5'=promotor
-3'= provides signal sequences for polyadenylation (addition of poly-A tail)
-LTR are flanked by target-site direct repeats

Front 47

Non-retroviral retrotranposons lack ____.

Back 47

LTRs

Front 48

What are the 2 classes of non-retroviral retransposons?

Back 48

-LINES
-SINES

Front 49

What do LINES contain in retranpsosons that help with retrotransposition?

Back 49

Coding sequences (ORF1 and ORF2)

Front 50

Are LINES autonomous?

Back 50

Yes

Front 51

Why are SINES non-autonomous?

Back 51

-Do not encode protein and most likely depend on proteins produced by LINES to mediate their retrotransposition

Front 52

The Selfish Gene

Back 52

Genetic elements that retained the ability to move and may cause mutations

Front 53

Unequal crossing-over

Back 53

The result of meiotic homologous recombination that occurs when their is mis-alignment (unequal homologous recombination) and can produce hybrid

Front 54

What can arise from unequal crossing over?

Back 54

-the development of clusters

Front 55

Unequal sister chromatid exchange

Back 55

unequal homologous recombination between sister chromatids during meisosis

Front 56

Duplicative Transposition

Back 56

Re-integration of the duplicated copies of retransposons into other chromosomal locations resulting in an increase in copy number of sequences

Front 57

3 Ways to have Transposition-based Sequence Duplication

Back 57

-DNA tranposons are tranposed soon after they have been replicated to a region beyond the replication fork
-LINEs creating more copies of themselves through transcription, translation, and reverse transcriptase
-LINES can help create more copies of non-autonomous retrotransposons (ex. SINES)

Front 58

Why do retroelements tend to re-integrate into chromosomal regions with active gene transcription activity?

Back 58

-More open chromatin configuration

Front 59

Depending on the chromosome(s) on which re-intergration will take place and the orientation of the re-integrated element(s) what events may occur?

Back 59

-Intra-chromosomal direct repeat
-Inverted Repeat
-Inter-chromosomal Repeat

Front 60

Why do retroelements tend to re-integrate into chromosomal regions with active gene transcription activity?

Back 60

-More open chromatin configuration

Front 61

Depending on the chromosome(s) on which re-intergration will take place and the orientation of the re-integrated element(s) what events may occur?

Back 61

-Intra-chromosomal direct repeat
-Inverted Repeat
-Inter-chromosomal Repeat

Front 62

Why do retroelements tend to re-integrate into chromosomal regions with active gene transcription activity?

Back 62

-More open chromatin configuration

Front 63

Depending on the chromosome(s) on which re-intergration will take place and the orientation of the re-integrated element(s) what events may occur?

Back 63

-Intra-chromosomal direct repeat
-Inverted Repeat
-Inter-chromosomal Repeat

Front 64

Why do retroelements tend to re-integrate into chromosomal regions with active gene transcription activity?

Back 64

-More open chromatin configuration

Front 65

Depending on the chromosome(s) on which re-intergration will take place and the orientation of the re-integrated element(s) what events may occur?

Back 65

-Intra-chromosomal direct repeat
-Inverted Repeat
-Inter-chromosomal Repeat

Front 66

____ _____ likely accounts for the high degree of polymorphism of short tandem loci in the human genome.

Back 66

-Replication Slippage

Front 67

In some species, duplication of an entire genome results in ______.

Back 67

Polyploidy (doesn't occur in humans)

Front 68

What type of event continually adds diversity to the genome?

Back 68

-Mutations

Front 69

What is the measure of relatedness of species?

Back 69

The number of orthologous genes

Front 70

Insertional Mutagenesis

Back 70

When the re-integration of a transposable element occurs within a coding, regulatory or signal sequence of a gene, the function of the gene is adversely affected

Front 71

Transcriptional Read Through; What kind of mutation can this cause?

Back 71

-LINEs give weak polyA signal causing the transcription to continue past the polyA signal of the LINE and only stopes when the next polyA signal is reached
-Exon Shuffling

Front 72

Processed Psudogene

Back 72

-Occurs when mRNA of a gene is erroneously reverse transcribed into a cDNA by the reverse transcriptase of a LINE
-the re-integrated coding sequence cannot be expressed because it lacks the requisite promoter or regulatory elements=pseudogene

Front 73

By increasing the number of copies of _____ ____ in the genome, significantly increase the likelihood of homologous recombination between different chromosomal regions.

Back 73

dispersed repeats

Front 74

What region on a chromosome is deleted in Sotos syndrome?

Back 74

Chromosome 5