Gene Mapping

Question 1

what is the chromosome theory? who proposed it along with genes as the basic unit of inheritance? when?

Answer 1

sutton and boveri in 1902 proposed chromosome is a linkage group of mendelian factors
morgan et al in 1920 proposed genes are in a linear sequence on the chromosomes, they can be mapped

Question 2

describe Morgan’s contribution to genetics and how his linkage studies worked

Answer 2

reasoned hereditary information must be arranged linearly on chromosomes, one of first nobel prizes in medicine in the field of genetics
measured distance btw 2 genes is measured in centimorgans (cM)
he described linkage concepts

Question 3

describe what crossover, recombination and linkage are

Answer 3

genes are said to be linked when they occur in close proximity to one another on the same chromosome
crossover = recombination that occurs multiple times at random locations during meiosis
if 2 genes are very close to e/o on a chromosome then they are tightly linked and will be unlikely to crossover

Question 4

what are the different polymorphic markers and linkage analysis used in genetics?

Answer 4

the first step in gene mapping is to establish linkage with a known polymorphic marker
this can be done by recombination mapping to determine whether the gene is near a particular marker
4 different types of polymorphisms
3 mill found as a result of HGP
examples: southern blot

Question 5

dzs caused by TEs?

Answer 5

hemophilia A and B, severe combined immunodeficiency, porphyria, predisposition to CA, Duchenne muscular dystrophy

Question 6

LINE1 TEs that land on factor VIII cause what?

Answer 6

hemophilia

Question 7

insertion of L1 into APC genes causes what?

Answer 7

colon cancer

Question 8

what are traditional gene maps?

Answer 8

traditional maps with physical locations of gene based upon sequence of nucleotide base pairs

Question 9

what are epigenomic maps?

Answer 9

physical locations of genes but “annotations” or marked locations where modifications are made above base pair sequences altering, activating, repressing, winding/unwinding and opening/closing sequences

Question 10

what are cancer genomic maps?

Answer 10

locations of where “gain-of-function” and possible “loss-of-function” genes or epigenetic elements reside causing oncogenesis

Question 11

what are cancer genomic maps?

Answer 11

locations of where “gain-of-function” and possible “loss-of-function” genes or epigenetic elements reside causing oncogenesis

Question 12

3 types of traditional human genome maps?

Answer 12

physical maps - vary in resolution, measured in bps, genome sequence is ultimate physical map
cytogenetic maps - karyotype
linkage maps - distance is measured in the frequency of recombination coupling arrangements of alleles on linked genes

Question 13

3 types of traditional human genome maps?

Answer 13

physical maps - vary in resolution, measured in bps, genome sequence is ultimate physical map
cytogenetic maps - karyotype
linkage maps - distance is measured in the frequency of recombination coupling arrangements of alleles on linked genes

Question 14

if the gene of interest and the marker are on different chromosomes the alleles will remain together in an egg or sperm what %age of the time?

Answer 14

50% - thus they are unlinked

Question 15

if the gene of interest and the marker are on the same chromosomes the alleles will remain together in an egg or sperm what %age of the time?

Answer 15

50% - thus they are unlinked

Question 16

if the gene of interest and the marker are on the same chromosomes the alleles will remain together in an egg or sperm what %age of the time?

Answer 16

50% - thus they are unlinked

Question 17

if the gene of interest and the marker are close together on the same chromosomes the alleles will remain together in an egg or sperm what %age of the time?

Answer 17

crossover btw the 2 alleles is much less likely to occur and shows less than 50% recombination - thus said to be linked

Question 18

if the gene of interest and the marker are close together on the same chromosomes the alleles will remain together in an egg or sperm what %age of the time?

Answer 18

crossover btw the 2 alleles is much less likely to occur and shows less than 50% recombination - thus said to be linked

Question 19

distance btw genes is expressed how? cM is equal to what recombination frequency?

Answer 19

centimorgans (cM)
the cM is equal to 1% recombination frequency
physically 1 cM is ~equal to 1 million base pairs of DNA

Question 20

distance btw genes is expressed how? cM is equal to what recombination frequency?

Answer 20

centimorgans (cM)
the cM is equal to 1% recombination frequency
physically 1 cM is ~equal to 1 million base pairs of DNA

Question 21

what are restriction enzymes or restriction endonuclease? relation to palindromes?

Answer 21

enzymes which recognize a specific sequence of nucleotides and produce a double-stranded cut in the DNA
cuts are made to correspond to 4-8 bps, many of which are palindromic which correspond to nitrogenous base sequences btw complementary strands which when read from the 5’ to 3’ direction are identical

Question 22

4 different types of DNA polymorphisms?

Answer 22

1. RFLP (restriction fragment length polymorphism)
2. VNTR (variable number of tandem repeats)
3. STR (short tandem repeats)
4. SNPs (single nucleotide polymorphism)

Question 23

what are VNTRs? dzs that are characteristic? when it is used?

Answer 23

variable number of tandem repeats
these polymorphisms are a result of varying numbers of mini-satellite repeats in a specific region of the chromosome
repeat is flanked on both sides by a restriction site
ex: fragile X syndrome, Huntington’s dz
used for parental testing or DNA fingerprinting

Question 24

what are STRs? can be amplified and visualized how? how are they used?

Answer 24

Short tandem repeat polymorphisms (microsatellites)
specifically repetitive sequences in which the repeated unit is 4-6 bps long
can be amplified with PCR by using products of varying length which can then be visualized on agarose gel electrophoresis
distributed throughout the chromosomes = very useful in mapping genes
used in paternity testing and in forensic cases as well as gene mapping

Question 25

what are SNPs? occur how often? can be typed/identified how? how many changes caused by SNPs in our genome, how many of these deleteriously impact the gene and how many of these are lethal?

Answer 25

represent nucleotide positions in the human genome where only 2 nucleotides are found
occur about once every 1000 bps
can be typed by pCR amplification and identification by sequencing or through probes on DNA chips
of our 20-25k genes, 2000 have SNPs, of those 200 deleteriously impact the gene, of those 5 are lethal if recessive homozygous

Question 26

what is DNA profiling? what does it use?

Answer 26

technique employed to assist in the identification of individuals by their respective DNA profiles
it uses repetitive sequences that are highly variable called variable number tandem repeats, specifically identify short tandem repeats

Question 27

what are DNA profiles?

Answer 27

encrypted sets of numbers that reflect a person’s DNA makeup which can also be used as the person’s identifier
used in parental testing and criminal investigation