Indiana University-Purdue University Indianapolis (IUPUI) / Population genetics has been revolutionized by the advent of high-throughput
sequencing (HTS) methods in the 21st century. Modern day sequencers are now
capable of sequencing entire exomes and genomes at unprecedented speed and
accuracy. An explosion of bioinformatics software and data analysis tools now
makes sequencing accessible for gene discovery in both rare Mendelian and
complex disease. Family-based sequencing studies in particular have great
potential for elucidating the genetic basis for many more diseases.
We apply both whole exome and genome sequencing to three different cases of
familial disease: intracranial aneurysm (IA), Parkinson disease (PD), and X-linked ataxia dementia (XLAD). IA and PD are both common, complex traits that
inflict a devastating disease burden worldwide, mostly due to few effective
therapeutic interventions. Little of the heritability of both IA and PD has been
explained to date, especially as it relates to the impact of rare variation on
disease. XLAD is an extremely rare neurological disease described thus far in
one kindred. Although promising results have been achieved through previous
genetic study designs, the causative gene has not yet been identified. For all
three diseases, HTS offers an opportunity to explore the role of rare variation in
disease pathogenesis. In each study, we explore the opportunities and
challenges of family-based HTS for different disease models. The work presented herein contributes effective practices for study design, analysis, and
interpretation in a rapidly growing field still replete with questions about how best
to implement HTS in studying familial disease.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/7921 |
| Date | January 2015 |
| Creators | Farlow, Janice L. |
| Contributors | Foroud, Tatiana |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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