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Genetics PMY-3 > Chromosome Mapping In. Eukaryotes > Flashcards

Chromosome Mapping In. Eukaryotes Flashcards

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1
Q

How did scientists study chromosomes before the whole genomes were known?

A

Scientists could isolate chromosomes in metaphase and identify the individuals chromosomes by staining them with dye to get a banding pattern

Scientists worked on identifying regions of the chromosome that they called “markers” and recorded the locus

Now that we have sequenced the genome, we can assign the genes to the appropriate regions of the chromosome to complete the map

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2
Q

How did the original scientists figure out which genes were on which chromosomes?

A

Chromosome mapping: genes responsible for phenotype were studied

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3
Q

What can be shown by test crosses?

A

If we perform test crosses, genes which are found close together the same chromosome, they are said to be linked

Original genetic studies showed that if multiple genes were on the same chromosome, they would be transmitted as a single unit

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4
Q

What does it mean to be”segregating together”?

A

If genes on the same chromo are close together, they are usually transmitted together, and this is called SEGREGATING TOGETHER

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5
Q

What does it mean to be “segregating away”?

A

If genes on the same chromosome and far from each other, they have a good chance of a recombination event happening between them and they DO NOT transmit together, and this is called segregating away

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6
Q

What is the frequency of crossing Over between any two loci? How did this aid the scientific community?

A

The frequency of crossing over between any two loci on a single chromosome is proportional to the distance between them 1% =1 mu(map unit)

This correlation allowed early scientists to construct chromosome maps which indicated the relative locations of the genes on the chromosomes

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7
Q

How did crossing over in Meiosis 1 aid scientists?

A

This crossing over in meiosis 1 results in the reshuffling/recombination of the alleles between homologs

Scientists used this to map out a chromosome and decipher how alleles are organized on a chromosome based on the probability of a crossover occurring between any two given alleles

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8
Q

What is linkage?

A

Two genes on a single pair of homologs; exchange occurs between two non sister chromatids

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9
Q

What does independent assortment result when two heterozygous genes are on two different pairs of chromosomes? (Scenario A)

A

Independent assortment: two genes on two different homologous pairs of chromosomes

Results of gamete formation when two heterozygous genes are on two different pairs of chromosomes

4 distinct gametes
AB
Ab
aB
aB
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10
Q

What does independent assortment result in when two heterozygous genes are on the same pair of homologs, but with exchange between nonsister chromatids?

A

result in when two heterozygous genes are on the same pair of homologs, but with exchange between nonsister chromatids

4 distinct gametes:
AB
Ab
aB
ab

If two linked genes (on same chromosome) are far apart, there is almost always be recombination between non sister chromatids and up to 50% of the gametes will have recombination

  • 1:1:1:1 ratio of the 4 gametes
  • Problem: similar results to scenario A with two unlinked and independently assisting genes
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11
Q

What happens if two linked genes are far apart?

A

If two linked genes (on same chromosome) are far apart, there is almost always be recombination between non sister chromatids and up to 50% of the gametes will have recombination

  • 1:1:1:1 ratio of the 4 gametes
  • Problem: similar results to scenario A with two unlinked and independently assisting genes
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12
Q

What are the results of gamete formation when two heterozygous genes are on the same pair of homologs with no exchange between them?

A

results of gamete formation when two heterozygous genes are on the same pair of homologs with no exchange between them

-2 distinct gametes, only parental/nonsister cross over gametes

AB
ab

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13
Q

How much crossing over and recombination occurs in each tetrad?

A
  • During mitosis, a limited number of crossing over and recombination occurs in each tetrad
  • Recombination occurs randomly along the length of the tetrad
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14
Q

If crossing over occurs 100% of the time, how much of the gametes are rearranged?

A

Only 50% of the gametes are rearranged

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15
Q

The closer two loci are to each other…

A

The less likely that a single crossover will occur between them

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16
Q

What are map units?

A

Percentage of rearranged gametes

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17
Q

What is the max number of % recombination and map units between two genes on the same chromosome?

A

50%

This suggests that a chiasma is formed between two genes 100% of the time

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18
Q

Two nonsister chromatids have rearranged. Two parental non-sister chromatids are unchanged….

A

This would appear as independent assortment

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19
Q

Single crossover occurs between two nonsister chromatids. What is the first possible scenario of the resulting gametes?

A

The exchange does not alter the linkage between the alleles of the two genes

Only parental gametes are formed

AB
ab

The exchange is undetected

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20
Q

Single crossing over occurs. What is the second possible outcome ?

A

The exchange separates the alleles of the two genes

Recombinant gametes are detectable:
AB
Ab
aB
ab

The percentage of recombinant alleles gives an idea of how close/far alleles are from each other

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21
Q

How were flies to find out two genes were linked?

A

Each parent is homozygous for the alleles eye color and thickness of wing veins

Normal wild type is dominant hv+ and bw+ (thin veins with red eye) and this is what F1 inherits

F1 is interbred

F2 generation produces 1:2:1 phenotypic and genotypic ratio

This is characteristic of complete linkage when the genes are very close together

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22
Q

In linkage ratio testcross, what is the zygosity of the parent?

A

Testcross parent Homozygous for both alleles

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23
Q

When testing for linkage, what is the test cross progeny?

A

Test cross progeny: 1:1 ratio:

  • thin vein/brown eye fly
  • heavy vein/red eye fly
24
Q

What does linkage ratio test cross test for?

A

Confirms complete linkage of the genes

We can call this a “linkage group”and the genes are on the same chromosome

25
Q

What phenomena was described by Thomas. H Morgan and student Alfred. H Sturtevant?

A

Morgan’s work with one gene on X chromosome led to the description of X-linked inheritance

Probability of recombination between two genes along a chromosome is related to distance between genes-described in 1911

26
Q

How did Thomas H. Morgan’s work lead to information of crossing over?

A

Morgan’s work with two genes on the X chromosome led to puzzling results, explanation led to the description that Chiasmas represent points of genetic exchange to form the recombinant gamete

Proposed that two genes located relatively close to each other on the same chromosome are less likely to have a chiasma form between them and exchange genetic information

27
Q

Who was Calvin Bridges?

A

He was also a student in the “fly room” and earned his PhD there(this is the Polytene chromosome guy)

28
Q

Describe an experiment to test distance between y and w genes on X chromosome

A

-Female parent has homozygous recessive alleles, male parent has dominant alleles

  • If F1 is female, they will have one X chromosome (with recessive alleles) from mom and chromosome from dad with the dominant alleles
    • expressed the dominant alleles
  • If F1 is male, they can only get recessive alleles mom and then the Y chromosome from dad
    • expressing the recessive alleles
29
Q

Explain the reason for the results of the fruit fly X chromosome experiment (y and w genes)

A

The Y and W genes are so close together that they usually segregate together, 99.5% of the time

0.5% of the time, there is recombination between Y and W alleles

30
Q

Describe the experiment on distance between y and m genes on X chromosome: F1

A

-Female parent has homozygous recessive alleles, male parent has dominant alleles

  • if F1 is female, they will have one X chromosome (with recessive alleles) from mom and chromosome from dad with the dominant alleles
    • Expressed the dominant alleles
  • if F1 is male,they can only get recessive alleles mom and then the Y chromosome from dad
    • Expressing the recessive alleles
31
Q

Explain the reason for the results between the flies for the y and m genes

A

The w and m genes have some distance and they often segregate together, 65.5% of the time

34.5 of the time, there is recombination between Y and W alleles

32
Q

Explain the frequencies for recombination yellow(y), white (w) and miniature (m)

A

A yellow and miniature cross was similarly performed and the results of the three experiments

  1. Yellow, white 0.5%
  2. White, miniature 34.5%
  3. Yellow, miniature 35.4% (this experiment was not shown)

Frequencies also called map units

Data suggest yellow and white genes are very close, and that white gene is closer to miniature gene than the yellow gene is

33
Q

What are the problems with performing X chromosome test cross on humans?

A
  • not ethical to perform carefully planned crosses with humans
  • humans do not produce large number of offspring
34
Q

What two techniques were developed to create human chromosome maps?

A

LOD score analysis

Somatic cell hybridization

35
Q

Briefly describe LOD score analysis as a means of human chromosome mapping

A

LOD score analysis relied on pedigree analysis of large families

  • traits determined by genes on the X-chromosome result in characteristic pedigree
  • Autosomal traits more difficult
36
Q

Briefly Describe somatic cell hybridization as a means of creating human chromosome maps

A
  • in the 1960s, somatic cell hybridization aided in the assignment of genes to their respective chromosome
  • Two cells in culture can be fused into a single hybrid cell
37
Q

What does LOD score mean?

A

Logarithm of Odds score, is a statistical test used in genetic linkage analysis

38
Q

What does the LOD score do?

A

Compares the probability of obtaining the test data if two loci are linked to the probability of obtaining the test data if the two loci are not linked

Extensive pedigrees, when available, allowed to conclude that two genes under consideration are closely linked (rarely separated in crossover)

39
Q

What do calculations of LOD score predict?

A

Calculations predict:

  • two traits are linked and segregate together
  • if the two traits are unlinked and show independent assortment

The probability is converted to to the logarithm

Traditionally a LOD score of 3.0 and above indicates linkage, 2.0 and below argues against linkage and in between score are inconclusive

40
Q

What about genes without identified gene products?

A

Three successes for gene mapping without knowing the gene product

  • the mutated protein giving rise to Huntington disease was mapped to chromosome 4
  • the mutated protein giving rise to cystic fibrosis was mapped to chromosome 7
  • the mutated protein giving rise to neurofibromatosis was mapped to chromosome 17
41
Q

What are DNA markers?

A

DNA markers were recognized by scientists studying recombinant DNA techniques (cutting and pasting DNA from different sources together)

Earliest examples RFLPs and Microsatellites and SNPs

42
Q

What are restriction endonucleases?

A

Restriction enzymes which cut DNA at particular sites on the DNA

Isolated from microbes

DNA is the same on the top strand as it is on the bottom strand in the 5’ to 3’ direction

43
Q

What does RFLP stand for?

A

Restriction fragment length polymorphisms

44
Q

What are polymorphisms?

A

Most people in the world have a region of DNA that is cut by a restriction endonuclease two times

People who have a change in their DNA yielding an extra cut site in the homologous region, we call this a polymorphism

45
Q

What are RFLP?

A
  • Scientists can identify the persons who have this polymorphism(extra cut site) by analyzing their DNA
  • We call this landmark a marker if the location is known
  • Scientists have identified thousands of these RFLP markers and many have linkage to genes of interest
46
Q

What are Microsatellites?

A

Short repetitive sequences, also refferred to as tandemly repeated DNA or STRs- short tandem repeats

1-10 base pairs tandemly repeated = ‘micro’ satellite

Repeats 5-50 times

47
Q

Where can microsatellites be found? How can Microsatellites be found?

A

Microsatellites are found throughout the genome

May be identified by the length of repeats and even by the DNA that flanks them

48
Q

What do SNP stand for?

A

Single Nucleotide Polymorphisms

49
Q

How much SNPs have been found?

A

Several millions of SNPs, “snips” have been found

50
Q

What have SNPs been used for?

A

Used by geneticists to identify and locate related genes

51
Q

How much SNPs are found in the population?

A

These DNA changes are found in at least 1% of the population and majority are not involved in disease

52
Q

Describe the association of SNPs and diseases

A

Some SNPs have shown an association with a disease or trait of interest so it helps geneticists IDENTIFY and LOCATE genes of interest

53
Q

Give a history of RFLPs as associated with diseases

A

In 2007, using SNPs as DNA markers, associations between 24 genomic locations were established with seven common human diseases (the gene responsible was unknown)

In each case, inherited susceptibility was mapped to a specific chromosome and led to the identification of a specific gene

54
Q

How do causative SNPs cause diseases?

A

Causative SNPs in a gene

Changes the amino acid sequence of the gene product (protein) and is the cause of a disease

55
Q

Majority of SNPs not the cause of disease…

A

But just a marker that linked to the defective gene

The markers are close to the gene so there is a low probability of crossover between the disease allele and the marker

Genetics PMY-3 (27 decks)

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