Fall Research Expo 2020

Investigating the Frequency of Copy Number Variants according to Ancestry in an Unselected Population

It has been established that copy number variations (CNVs) in a genome may result in a phenotypic expression, if the CNV is large enough. However, the mechanisms and full effects of CNVs are still being explored. Many of the studies that have been conducted use populations with known disorders. As a result, de novo CNVs have been recognized as a significant risk factor for Autism Spectrum Disorder and it has been determined that certain CNVs can contribute to the risk for, or the protection from, schizophrenia. This research aims to look at the burden of CNVs in unselected populations, or those not affected by known disorders, with the intent to observe the unbiased effects of CNVs on neuropsychiatric function. Additionally, we looked at the burden of CNVs as it differs across White British (N=385,517), Other European (N=51,325), South Asian (N=8849), and African (N=8,447) ancestry groups. The sample for this study was taken from the UK Biobank, which consists of information from almost 500,000 people between the ages of 40-69. Through calculating the mean pLI and mean LOEUF scores with respect to ancestries, it was determined that the overall burden of CNVs does not differ between ancestry groups. Additionally, we were able to identify six specific CNVs that differed in frequency across ancestry groups. The six included: 13q12del(CRYL1) (p = 1.518E-03), 15q11.2del (p = 1.704E-05) , 15q11.2dup (p = 6.504E-05), 15q13.3dup(CHRNA7) (p = 7.029E-07), 2q13del(NPHP1) (p = 1.517E-04), and 2q13dup(NPHP1) (p = 6.062E-27). With our observations, we were able to conclude that CNVs are present at appreciable frequency in “healthy” populations and that the frequency of individual CNVs differs by ancestry. To further this work, we have looked at previous publications to determine if our significant CNVs have had significant phenotypic effects.

PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023
Advised By
Join Alexys for a virtual discussion
PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023
Advised By

Comments

Great project and wonderful presentation, Alexys!  You mention that it would be useful to repeated your analyses using another sample set or database.  Does such a thing exist? 

Fascinating project! Great job to you and your team. Although you did not find significant trends when sorting by ancestry, I'm wondering if it is possible to see trends based on geography or environment, as those factors can also affect genetics. When you expand to analyzing more diverse genomes, is that something you are interested in investigating as well?