1. Deletions Project Tom Carpel 903273210 CS CM124 6/11/2008

2. What Are Deletions? How Do They Occur? ¤ Genetic Mutation ¤ Part of a chromosome is missing ¤ Caused when segments break apart but do not rejoin ¤ Often happens in crossing over during meiosis

3. How do deletions occur? a.A chromosome b.2 breaks; don’t rejoin c. External segments rejoin a.b.c.

4. Significance ¤ Identifying deletions is important ¤ Could lead to a frameshift mutation – nonfunctional proteins ¤ Cause some serious genetic diseases: male infertility, muscular dystrophy, Cri du Chat (“cry of the cat”), etc. ¤ Linked to Cancer gene inactivation ¤ Some deletions unrelated to diseases, need to study further, have a greater understanding

5. Detecting Deletions ¤ A SNP genotype with a deletion always looks homozygous: or

6. Detecting Deletions ¤ Mendelian Inconsistencies: ¤ Child’s genotype is impossible given parents’ genotypes ¤ If the child has a homozygous recorded genotype – could be a deletion

7. Detecting Deletions ¤ Deletions can be identified when many Mendelian inconsistencies occur in a row ¤ Single or few inconsistencies are probably due to a genotyping error

8. The Project ¤ Find deletions in individuals ¤ Use HapMap data with parents-child trios ¤ Sliding window over adjacent SNPs ¤ look for Mendelian inconsistencies ¤ Need at least 10 consecutive inconsistencies to constitute a deleted region

9. The Project ¤ Goal: To be able to find deleted regions that are known, hopefully some of the same ones that Erik Corona found ¤ Difficulties: ¤ The format of the HapMap data – parsing ¤ The program will not detect deletion regions where only several SNPs are inconsistent

10. The Project ¤ Identify where a deleted sequence begins and ends for each individual ¤ Use individuals’ results to find common deleted regions in a population ¤ For example: Took 3 trios out of CEU population with no inconsistencies. Inserted 11 consecutive inconsistencies:

11. The Project – Identify Prevalent Deletions in Population Example position POP:CEU [NA12003 NA12004 NA10838 NA12005 NA12006 NA10839 NA12056 NA12057 NA10851] 118466311 CC CC CC CC CC CC TT CT CC 118466994 CC CT TT CT CT TT CC CC CC 118467652 CT TT CC TT TT TT TT TT TT 118470868 AT AA TT AA AA AA AA AA AA 118471179 GG TT TT GG GG GG TT GT TT 118471271 GA GG AA GG GG GG GG GG GG 118471329 TC CC TT CC CC CC CC CC CC 118471381 TT GG GG TT TT TT TT TT TT 118471712 TT AT AA TT TT TT TT TT TT 118472013 TT TC CC TT TT TT CC CT CC 118472074 TT AA TT AA AA AA AA AA AA 118472557 CT CC TT CC CC CC TT CT TT 118473803 CT CT TT CT CT TT TT CT TT Snippet of the input to the program. 11 contiguous inconsistencies were introduced to the data.

12. The Project – Identify Prevalent Deletions in Population Example

13. The Project – Run on actual HapMap Data ¤ Run the program on the CEU (Utah residents with Northern and Western European Ancestry) data from HapMap Build 36. Specifically encode region ENr113: 4:118466103..118966103 ¤ Did not find any deletions, but found scattered inconsistencies ¤ Confirmed by tracing through the data

14. The Project – Run on actual HapMap Data

15. Future Work ¤ Project can be expanded to include criterions for telling when very large sections of deletions are related to Cancer ¤ Include further analysis to identify whether a series of inconsistencies is due to an actual deletion or a genotyping error

16. Conclusion ¤ Finding deletions ¤ Mendelian Inconsistency ¤ Homozygous genotype recorded ¤ Multiple consecutive inconsistencies ¤ Can find all inconsistencies and possible deletions in HapMap data using the program ¤ Learn more about correlation between deletions and genetic diseases

17. Thank You! Questions? Comments? Concerns?