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Kaitlin Samocha

@ksamocha

Oct 27

Maureen Pittman #ASHG22: Oligogenic inheritance describes situations were there are some loci (more than one, less than thousands) that contribute to a disease.

Congenital heart disease (CHD) is potentially one of these situations.

Maureen Pittman #ASHG22: Example of a family where GATA6 was passed on from an unaffected parent to a child with CHD. Common variants don't seem to contribute much -- could it be due to other rare variants?

Maureen Pittman #ASHG22: Oligogenic genes are presumed to have related functions and could potentially compensate for each other or could interact, etc.

But finding oligogenic gene examples has been hard due to all of the combinations you have to test.

Read 11 tweets

Kaitlin Samocha

@ksamocha

Oct 27

@grahamserwin

Graham Erwin (@grahamserwin) #ASHG22: Half of the human genome is repetitive, most are transposons but about 3% is made up of tandem repeats. Tandem repeats cause >40 human diseases.

@grahamserwin

Graham Erwin (@grahamserwin) #ASHG22: Friedreich's ataxia is caused by a triplet expansion in the first intron of FXN gene. Patients have 70++ repeats, which leads to lower expression/protein levels.

@grahamserwin

Graham Erwin (@grahamserwin) #ASHG22: Polyamides bind to DNA specifically and are very small (cell permeable). Prior example to tie one of these to a factor that would lead to higher transcription.
pubmed.ncbi.nlm.nih.gov/29192133/

Now want to target other repeats.

Read 7 tweets

Kaitlin Samocha

@ksamocha

Oct 27

Scott Younger #ASHG22: Genomic Answers for Kids (GA4K). Currently have >10k subjects enrolled and have returned ~1k diagnoses.

Focus here is large scale assays, specifically establishing a protocol to do patient-derived iPSC reprogramming at scale. Have generated 250 iPSC lines

Scott Younger #ASHG22: Using antisense oligonucleotides (ASOs) to modulate gene expression. Proof of their use in TNNT2 gene.

Scott Younger #ASHG22: Robust restoration of dystrophin expression in DMD-patient organoids when applying a DMD-targeting ASO. Phenotypes restored as well (beating cells in dish).

Read 5 tweets

Kaitlin Samocha

@ksamocha

Oct 27

@yi_ding_

Yi Ding (@yi_ding_) #ASHG22: Polygenic scoring estimates genetic value by aggregating signal across many loci. Potential for polygenic scores has already been well established -- but so have the challenges, especially the low accuracy in non-European populations.

@yi_ding_

Yi Ding (@yi_ding_) #ASHG22: Genetic ancestries are continuous and cluster-free.
- By forcing clusters on ancestry, miss inter-individual variability.
- The boundaries between these groups is also fairly arbitrary.
- Clustering also typically removes any unclassified individuals

@yi_ding_

Yi Ding (@yi_ding_) #ASHG22: Goal is to evaluate PGS accuracy at an individual level.

Using genetic distance to characterize and individual's unique position (Euclidiean distance) in genetic ancestry continuum. Also evaluating individual PGS accuracy.

Read 6 tweets

Kaitlin Samocha

@ksamocha

Oct 27

Now on in the plenaries -- Catherine Robertson #ASHG22: Beta cells in the islets of the pancreas produce insulin. Type 1 diabetes is defined by loss of insulin production due to cell death or dysfunction. Disease risk is both genetic and environmental.

Catherine Robertson #ASHG22: Many common variants tied to T1D, but causal variants are hard to find -- some seem to impact cis-regulatory processes.

Now doing single cell/nuclei RNA-seq, ATAC-seq, and 5' RNA-seq.

Catherine Robertson #ASHG22: Nice overlap of all three data types for the PDX1 locus. Can describe regulatory processes across various cell types or stimuli +/-.

Hypothesis: T1D variants alter regulatory processes in islets.

Read 4 tweets

Kaitlin Samocha

@ksamocha

Oct 26

@Jazlyn_Mooney

Jazlyn Mooney (@Jazlyn_Mooney) #ASHG22: Want to trace the genealogical ancestors in African American individuals. 1870 census was the first collected to have more detailed information on African Americans in the US -- but still not a lot. Many do not know their roots.

@Jazlyn_Mooney

Jazlyn Mooney (@Jazlyn_Mooney) #ASHG22 draws a distinction: genealogical and genetic ancestors are not the same.

Can use ancestry proportions from the present to estimate the number of ancestors from each source population in past. Implementing a mechanistic model of admixture

@Jazlyn_Mooney

Jazlyn Mooney (@Jazlyn_Mooney) #ASHG22: Model estimates the number of genealogical ancestors. Applying to African American ancestry individuals. Slave trade moved many individuals to the Americas. Shows time epochs on the model (slave trade, slavery, segregation era).

Read 5 tweets

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