Problem Set 6

PLAS 215 – Problem Set 6 Lesson #6 Gene Mapping PLAS 215 Genetics 1. Predicting breast cancer with linked genes. Backstory : Henry Lynch, an oncologist working for Creighton University School of Medicine in Omaha, observed in the 1980s that many of the patients he saw with breast and ovarian cancer were members of the same family. He was among the first to propose that there were genes that, when mutated, created alleles that put members of these families at higher risk of getting certain kinds of cancer. In the 1980s, human geneticists started to map these genes to specific loci on the human chromosomes. D17S74 is a locus from chromosome 17 that can be tested at the DNA level to see if people have DNA differences. We will call ‘D’ one version of this DNA locus and ‘d’ the other. Family members whose mothers had breast-ovarian cancer were tested for their D,d genotype. Their diagnosis for breast-ovarian cancer was also determined. Data from two families is below. Both families: mothers were Dd and fathers were dd and it was assumed the mother could pass on an allele for higher breast-ovarian cancer risk to half of her daughters. 1a. Which of the families appear to have an ovarian cancer predisposition gene linked with the D17S74 locus? Family A Family B Both Neither 1b. Based on the data, show how you would estimate that there are about 6 map units between the D,d and the ovarian cancer locus? 1 DNA test (Family A) Cancer status (Family A) Number Dd No cancer 8 Dd Ovarian/breast cancer 12 dd No cancer 10 dd Ovarian/breast cancer 14 44 DNA test (Family B) Cancer status (Family B) Number Dd No cancer 29 Dd Ovarian/breast cancer 1 dd No cancer 3 dd Ovarian/breast cancer 31 64

PLAS 215 – Problem Set 6 1c. ORAL QUESTION PREPARATION. We now know from inheritance studies and gene discovery research that there are two loci on human chromosomes that have genes which control the risk for ovarian/breast cancer. BRCA2 is on chromosome 17. BRCA1 is on chromosome 13. You will use this visual to help answer an oral question which is based on question 1.  The D,d locus is a DNA sequence found on chromosome 17. Which breast cancer gene would be INDEPENDENTLY ASSORTING WITH THE D,d locus? The breast cancer gene being passed on in Family A or Family B? Use the chromosome pictures to explain.  What is a map unit?  What is the highest frequency of recombinant gametes you would expect to observe when tracking the inheritance of genes from two loci like we are doing in question 1? 2

PLAS 215 – Problem Set 6 2e. Additional mapping studies were conducted to discover which gene mapped to chromosome 17 might be the breast cancer gene. Based on the data below, which is the likely candidate….ie the tested gene is actually the one causing cancer. Cross was parent with cancer Er / eR DNA damage repair enzyme (E,e) Offspring Ee ; no cancer 0 Ee: breast/ovarian cancer 29 ee: no cancer 31 ee: breast/ovarian cancer 0 60 4 RARA (R,r) Offspring Rr ; no cancer 28 Rr: breast/ovarian cancer 1 rr: no cancer 3 rr: breast/ ovarian cancer 28 60

PLAS 215 – Problem Set 6 3. Mapping the color blindness allele. Color blindness is not a disease but is an X-linked trait. The gene for color blindness is recessive (b) and the normal color vision allele is dominant (B). Geneticists find women who are heterozygous at the A,a; B,b and I, i loci and all have the same arrangement of these genes on their X chromosome. They determine the phenotypes among the 248 sons of these trihybrid women to generate the following data. Trihybrid women’s gametes Numbe r AB BI AI ABI 8 - 8 8 ABi 84 - - - AbI 24 24 - 24 Abi 2 2 2 - aBI 4 4 4 - aBi 34 34 - 34 abI 82 - - - abi 10 - 1 0 10 248 64 2 4 76 3a.Draw a map representing the distances between the A, B and I loci. Use the above mapping data to place the B locus (blindness) on map to the right if the A locus is ALD and the I locus is SCID. 3b.Based on your chromosomal map to the left, explain why the hemophilia A trait is independent of the DMD trait, even though the genes controlling these traits are on the 5

PLAS 215 – Problem Set 6 4. Gene mapping in soybean. Backstory : Thousands of acres in Nebraska have high pH soils. Some soybean genotypes grow very poorly in these soils because of iron chlorosis. There is Fe in the soil, but the soybean plant cannot extract it in high pH. Some genotypes have the ability to grow well in these high pH soils. There is a mysterious gene that controls this ability. Teams of breeders and geneticists like the UNL team above work together to learn more about this gene. Mapping this gene can help the breeder make selections and eventually help soybean geneticists discover the gene. Use the data below to map. H,h is the high pH tolerance gene. Plants that are H_ tolerate the high pH (are green), hh plants get the Fe deficiency phenotype. F,f; G,g; R,r; T,t and Y,y loci are known DNA markers. Determine the map units between the F,f; G,g; R,r; T,t and Y,y loci to generate a map in order to find the best marker for the H locus. 4a. Cross #1 -- FfGgHh X ffgghh Gamete from the trihybrid FGH 48 FGh 168 FgH 2 Fgh 282 fGH 286 fGh 4 fgH 166 fgh 44 1000 Map the F,f ; G,g and H,h loci: Need some help? We’ve got some help for conducting 3 point crosses and why we have to add double crossovers . 7

PLAS 215 – Problem Set 6 4b. Cross #2 -- RrHh X rrhh Gamete from the dihybrid: RH 23 Rh 227 rH 233 rh 17 500 Map distance between the R,r and H,h loci: Other mapping studies were done when the plants could not be scored for the H,h Fe chlorosis trait. 4c. Cross #3 – RT / rt X rrtt Gamete from the dihybrid: RT 289 rT 11 Rt 10 rt 290 600 Map distance between the R,r and T,t loci: 4d. Cross #4 – Gt / gT X ggtt Gamete from the dihybrid: GT 91 gT 206 Gt 214 gt 89 600 Map distance between the G,g and T,t loci: 4e.Draw a map of these loci and indicate the interval where you would expect to find the candidate gene for Fe uptake in high pH.   8

PLAS 215 – Problem Set 6 5. Using the Y chromosome to answer ancestry questions. The X and Y chromosomes pair up with one another during mitosis and meiosis. Today, the Y chromosome is often used to “track” genetic ancestry in males. Rumors circulated in the early 1800’s that Thomas Jefferson had children with Sally Hemings, an enslaved woman. Until more recently, there wasn’t any way to determine if the rumors were true. In 1998, researchers conducted genetic testing on male descendants in the Jefferson family and Hemings’ male descendants to solve the mystery. Why would geneticists choose to study males when solving this Jefferson mystery? 5a.Why can’t genetic information from Polly Jefferson (Thomas Jefferson’s known child) be used to solve this Thomas/Sally mystery? 10

PLAS 215 – Problem Set 6 5b.Why would it be difficult to create a linkage map for most of the loci on the Y chromosome? Use the term “crossing-over” in your answer. 5c. Use the marker table below from Cal State East Bay’s website that summarizes the genetic data from the Thomas/Sally mystery. Does the genetic data suggest Jefferson had a child with Sally? Marker No. Field Jefferson Descendants (5 tested) Eston Hemings Descendant (1 tested) John Carr Descendants (3 tested) Thomas Woodson Descendants (5 tested) 393 13 13 13 13 390 11 11 11 11 19 15 15 14 14 391 10 10 10 13 388 12 12 12 12 389A 04 04 05 05 392 15 15 13 13 389B 11 11 12 11 389C 03 03 03 03 389D 9 9 10 10 OPTIONAL resources for reading more about the genetics mystery -- PBS – A Primer on Jefferson DNA and The Genetic Genealogist 5d.Conduct some internet research. What are two other sources of DNA that can used to track ancestry (hint: one type of DNA is passed on maternally and the other can be used for all people)? 11