3. (22 points) Cancer as a contagion. The cancer cells of Tasmanian Devil Facial

Question

3. (22 points) Cancer as a contagion. The cancer cells of Tasmanian Devil Facial Tumor Disease (DFTD) are infectious and can be spread to an uninfected animal through the bite from an infected tumor cell carrying animal. DFTD was identified in 2006 by Pearse and Swift when they noticed that the karyotype from the tumor cells was markedly different from the host animal cells. The tumor cells in genetically different affected animals, also appeared to share the same origin. High throughput DNA sequencing confirmed these findings of a transmissible tumor (Murchison et al. 2012) as the tumor genotype was unlikely to have arisen from somatic mutation and clonal expansion from the host genotype. Recently, as reported in Pye et al (2016), a second transmissible cancer, DFT2 has been found in Tasmanian devils. DFT2 causes the same sort of facial tumors as the first tumor type (DFT1), but is cytogenetically distinct from DFT1 Females Males DFT1 DFT2 I Homozygous (REF Homozygous (ALT Hotorozgyous Unrelated DFT2 hosts DFT1 DFT2 devil Alleles L 190 194 E 271 273 274 D 142 144 N 201 203 C 172 174 176 M 159 161 221 223 F 244 246 K 157 1159 (a) Panel A shows genotyping of 10 X-linked SNPs from 37 females, 37 males and DFT1 and DFT2 tumor samples. Animals (or tumor samples) are represented by the individual columns and each SNP is represented by a row. Color coding refers to whether the anima/sample is homozygous (matching the reference sequence), homozygous (with an alternate sequence) or heterozygous at that SNP

Explanation / Answer

Question (a):

Why DFT2 homozygous at all of the listed SNPs?

This can be potentially of male origin.

Please note that the results are SNP genotyping of X-chromosome variants. Females have two X chromosomes. So, they can be homozygous or heterozygous for an SNP on X chromosome. Males have one X chromosome. So they are genetically hemizygous for X chromosome. In high throughput sequencing we find what proportion of reads is showing SNV. If all reads show SNV, we call it homozygous for SNV.

Also note that DFT1 can be of female origin. All SNVs are heterozygous.

Question (b):

What is a microsatellite genotype and what is it used for?

Microsatellite genotyping is identifying the length of microsatellite markers in an individual or specimen. It is used in DNA fingerprinting to detect DNA of suspect or resolve paternity cases. Microsatellite profile of an individual is unique and does not match with any other individual.

In this study, they took DNA isolated from healthy devils, DFT1 tumors, DFT2 tumors and DFT2 host devil (a devil infected with DFT2) and checked microsatellite profile. If we compare, microsatellite profiles, we will know if DFT1 and DFT2 originated from same individual or not.

What conclusions can ………..genotype?

DFT1 and DFT2 tumors have different origin. We would find that microsatellite lengths are different between DFT1 and DFT2 for many markers (eg. E, D, N, C, J, F and K).

Two tumors of DFT1 were analyzed. Those are 87T and 88T. Both have same origin (because both have exactly same profile).

Two tumors of DFT2 were analyzed. Those are RV-T and SN-T. Both have same origin (because both have exactly same profile).

Question (c):

Which haplotypes are ……. In DFT1 tumors?

Sahal*46, *98 and *45.

Which haplotypes are ……. In DFT2 tumors?

Sahal*88.

Question (d):

Why is it surprising that one would recover DFT2 cells that differ in MHC from the DFT2

This question is not making sense. So, I am assuming the following would be the correct question.

Why is it surprising that one would recover DFT2 cells that differ in MHC from the DFT2 host?

It is surprising because host did not reject the tumor (here it is allograft) even though it has different MHC Class I antigens.MHC help in self and non-self recognition. Generally, if the body encounters cells expressing different MHC (foreign cell or graft), host T cells eliminate the foreign cell.

We can guess that probably DFT2 cells are not expressing the MHC on their cell surface. Then host T cells can not kill them.

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