Towards Making Identification of Noncoding Causes of Human Disease Routine
summary
Workflows move from GWAS hit to mechanism: a gestational‑hyperglycemia locus leads to cloning and enzymatic assay showing HKDC1 has low but real hexokinase activity, knockout is embryonic lethal and heterozygous mice show pregnancy‑specific glucose intolerance — a claimed first mouse model of gestational diabetes. Ultra‑rare cases reveal a 76 bp pseudo‑exon from blood RNA‑seq; CRISPR HDR editing in HEK293T screens ~500 clones to get 9 lines and produces a 90% reduction in PHKG2 activity. Structural hits include a 1.5 kb deletion found by nanopore and exon skipping confirmed by PacBio long‑read RNA. High‑throughput STARR‑seq assays ~500 million to a billion fragments and 10 million variants with reproducible enhancer peaks.
AI-written summary · about
chapters (7)
- 0:00Start
- 1:36An old example: gestational hyperglycemia
- 9:14Genetic diagnosis of rare disease Early therapeutic intervention increases lifespan and/or quality of life for many rare diseases.
- 10:28Glycogen Storage Disease Type IXC
- 20:11High-throughput genomic techniques to measure regulatory element activity
- 21:50Identifying genetic effects on regulatory element activity across the human population
- 23:56Population STARR-seq: Beta-globin locus
related talks
50mThe algorithm for precision medicine
01h 13mIntroduction to Regulatory Genomics and Epigenomics I: Intro to the Biology of Gene Regulation
38mBig data in personalised medicine
35mTranscriptional Enhancers - Looking out for the Genes and Each Other
17mBig data in personalized medicine
38mInterpreting Deep Learning Models Of Functional Genomics Data To Decode Regulatory Sequence...
39mIdentifying Disease Mechanisms Using Gene Networks as Priors
33mLong-Range Propagation of Genetic Effects in Molecular Networks