Medical genetics 2 of 2
-
Upload
ethan-perlstein -
Category
Documents
-
view
295 -
download
1
Transcript of Medical genetics 2 of 2
![Page 1: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/1.jpg)
Medical Genetics(2 of 2)
Last week: How did we clone a Mendelian disease gene?
This week: How does a Mendelian disease allele arise?
![Page 2: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/2.jpg)
Tay-Sachs Disease (TSD)
GM2 Gangliosidosis
![Page 3: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/3.jpg)
Bernard Sachs 1887
Konrad Sandhoff1965
Waren Tay1881
• Autosomal recessive degenerative disorder• Mutations affect a gene called HEXA (hexosamidinase) located on CHR 15• Infantile, Juvenile and Adult/Late Onset• First successful genetic screening
![Page 4: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/4.jpg)
Pathophysiology: lipid accumulation
![Page 5: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/5.jpg)
![Page 6: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/6.jpg)
![Page 7: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/7.jpg)
![Page 8: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/8.jpg)
![Page 9: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/9.jpg)
Why is the TSD carrier frequency so high?
Mycobacteriumtuberculosis
1278insTATC allele frequency is 0.0156 among Askenazi Jews
![Page 10: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/10.jpg)
Testing the heterozygote advantage model
No significant differences in mortalitybetween grandparents of carriers vs. non-carriers
![Page 11: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/11.jpg)
![Page 12: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/12.jpg)
Sanger sequencing (old school)
![Page 13: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/13.jpg)
“Jewish Fur Trader Hypothesis”
![Page 14: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/14.jpg)
Founder/Bottleneck Effect
![Page 15: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/15.jpg)
![Page 16: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/16.jpg)
![Page 17: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/17.jpg)
![Page 18: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/18.jpg)
![Page 19: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/19.jpg)
![Page 20: Medical genetics 2 of 2](https://reader036.fdocuments.in/reader036/viewer/2022081420/556e5e28d8b42a6a248b4856/html5/thumbnails/20.jpg)