Deletions Project

Tom Carpel903273210CS CM1246/11/2008

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

How do deletions occur?

a. A chromosomeb. 2 breaks;

don’t rejoinc. External segments

rejoin

a. b. c.

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

Detecting Deletions

¤ A SNP genotype with a deletion always looks homozygous:

or

Detecting Deletions

¤ Mendelian Inconsistencies:¤ Child’s genotype is impossible given parents’ genotypes

¤ If the child has a homozygous recorded genotype – could be a deletion

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

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

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

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:

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 CC118466994 CC CT TT CT CT TT CC CC CC118467652 CT TT CC TT TT TT TT TT TT118470868 AT AA TT AA AA AA AA AA AA118471179 GG TT TT GG GG GG TT GT TT118471271 GA GG AA GG GG GG GG GG GG118471329 TC CC TT CC CC CC CC CC CC118471381 TT GG GG TT TT TT TT TT TT118471712 TT AT AA TT TT TT TT TT TT118472013 TT TC CC TT TT TT CC CT CC118472074 TT AA TT AA AA AA AA AA AA118472557 CT CC TT CC CC CC TT CT TT118473803 CT CT TT CT CT TT TT CT TT

Snippet of the input to the program. 11 contiguous inconsistencies were introduced to the data.

The Project – Identify Prevalent Deletions in Population Example

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

The Project – Run on actual HapMap Data

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

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

Thank You!

Questions? Comments? Concerns?