Veera Rajagopal
@doctorveera.bsky.social
MBBS, MD, PhD | GWAS storyteller | Scientist at Regeneron | Human genetics & drug discovery in Neuroscience & Psychiatry
Congratulations!
March 20, 2025 at 12:16 PM
Congratulations!
There seems to be another companion manuscript with this one discussing the long read dataset in a much broader context. The current one is focussed on TRs. This data release marks exciting progress in human genetics in 2025. 9/
January 9, 2025 at 4:37 PM
There seems to be another companion manuscript with this one discussing the long read dataset in a much broader context. The current one is focussed on TRs. This data release marks exciting progress in human genetics in 2025. 9/
Interestingly, these extremely polymorphic repeat loci identified in humans are monomorphic in apes based on available data, suggesting that human-specific expansion. 8/
January 9, 2025 at 4:37 PM
Interestingly, these extremely polymorphic repeat loci identified in humans are monomorphic in apes based on available data, suggesting that human-specific expansion. 8/
This observation goes against the concept of mutation constraint: disease loci are usually depleted of variations. It seems for repeat loci it's more complex. 7/
January 9, 2025 at 4:37 PM
This observation goes against the concept of mutation constraint: disease loci are usually depleted of variations. It seems for repeat loci it's more complex. 7/
The second most polymorphic repeat at this same locus--CAG repeat in THAP11--is also disease-causing. 6/
January 9, 2025 at 4:37 PM
The second most polymorphic repeat at this same locus--CAG repeat in THAP11--is also disease-causing. 6/
For e.g., last year GGC exonic repeat in ZFHX3 was discovered (after nearly 25 years) to be the causal variant in SCA4 locus. The authors find that around the SCA4 locus, GGC repeat is the 5th most polymorphic repeat. 5/
January 9, 2025 at 4:37 PM
For e.g., last year GGC exonic repeat in ZFHX3 was discovered (after nearly 25 years) to be the causal variant in SCA4 locus. The authors find that around the SCA4 locus, GGC repeat is the 5th most polymorphic repeat. 5/
The authors suggest we can actually use this logic to identify causal repeat variants at unresolved disease loci. Just search for the most variable repeats within the linkage region and most likely one of them is the culprit. 4/
January 9, 2025 at 4:37 PM
The authors suggest we can actually use this logic to identify causal repeat variants at unresolved disease loci. Just search for the most variable repeats within the linkage region and most likely one of them is the culprit. 4/
Many interesting results in the preprint. One surprising revelation is the authors find that known pathogenic repeat loci are the most variable in the genome (of course, within the benign range). 3/
January 9, 2025 at 4:37 PM
Many interesting results in the preprint. One surprising revelation is the authors find that known pathogenic repeat loci are the most variable in the genome (of course, within the benign range). 3/
I remember hearing about this dataset first time at ASHG 2022. Great to see the data out finally. Using 1027 long read genomes, the authors have identified >3.6 billion TR alleles (!) at 1.7 million loci. 2/
January 9, 2025 at 4:37 PM
I remember hearing about this dataset first time at ASHG 2022. Great to see the data out finally. Using 1027 long read genomes, the authors have identified >3.6 billion TR alleles (!) at 1.7 million loci. 2/
Great News and Views explaining the background and discovery in simple accessible language by Sardar and Kutateladze.
www.nature.com/articles/d41...
www.nature.com/articles/d41...
Circadian rhythms are set by epigenetic marks in neurons
Exchanger enzyme modifies histones in histamine-releasing neurons.
www.nature.com
January 9, 2025 at 3:06 PM
Great News and Views explaining the background and discovery in simple accessible language by Sardar and Kutateladze.
www.nature.com/articles/d41...
www.nature.com/articles/d41...
Fascinating discovery and may have implications in psychiatric and sleep related disorders. I wonder how many more PTMs are there waiting to be discovered.
January 9, 2025 at 3:06 PM
Fascinating discovery and may have implications in psychiatric and sleep related disorders. I wonder how many more PTMs are there waiting to be discovered.
Addition and removal of histamine to histones in the neurons in brain circadian rhythm center seems to control the sleep wake cycle.
January 9, 2025 at 3:06 PM
Addition and removal of histamine to histones in the neurons in brain circadian rhythm center seems to control the sleep wake cycle.
This adds to the list of histone monoaminylations recently discovered (serotonylation in 2019, dopaminylation in 2020 by the same group of authors).
January 9, 2025 at 3:06 PM
This adds to the list of histone monoaminylations recently discovered (serotonylation in 2019, dopaminylation in 2020 by the same group of authors).
Another great discovery before we close the year, highlighting the underappreciated role of retroelements in human disease and traits. 5/
December 23, 2024 at 4:59 AM
Another great discovery before we close the year, highlighting the underappreciated role of retroelements in human disease and traits. 5/
This also would mean the target population for ASPA gene therapy (currently in trials by Myrtelle Inc.) might be much larger than expected. 4/
December 23, 2024 at 4:59 AM
This also would mean the target population for ASPA gene therapy (currently in trials by Myrtelle Inc.) might be much larger than expected. 4/
Unlike the recurrent mutations previously found, which were mostly restricted to Ashkenazi Jewish ancestry, the SVA insertion seems to be occurring across all ancestries, making it the most common cause worldwide. 3/
December 23, 2024 at 4:59 AM
Unlike the recurrent mutations previously found, which were mostly restricted to Ashkenazi Jewish ancestry, the SVA insertion seems to be occurring across all ancestries, making it the most common cause worldwide. 3/
Due to the limitations of short read sequencing, this mutation has remained hidden for more than 25 years since ASPA mutations were first characterized in individuals Canavan disease. 2/
December 23, 2024 at 4:59 AM
Due to the limitations of short read sequencing, this mutation has remained hidden for more than 25 years since ASPA mutations were first characterized in individuals Canavan disease. 2/
Reposted by Veera Rajagopal
Can't comment on the genetics but agree this is a huge "so what?" for clinical practice – we already use patient-specific trends for diagnosis and management and have for decades. The specific examples given in the article (like HCT and CKD) are... amusingly obvious.
December 17, 2024 at 3:10 PM
Can't comment on the genetics but agree this is a huge "so what?" for clinical practice – we already use patient-specific trends for diagnosis and management and have for decades. The specific examples given in the article (like HCT and CKD) are... amusingly obvious.
Reposted by Veera Rajagopal
Arguably the reason that GWAS for blood traits have ever worked is that we are proxying the individual set point. So yes the clinical discussion is neat. The genetic implications seem nil.
December 17, 2024 at 3:03 PM
Arguably the reason that GWAS for blood traits have ever worked is that we are proxying the individual set point. So yes the clinical discussion is neat. The genetic implications seem nil.
Likewise, the GWAS of blood count setpoints is almost the same as past GWASs of blood counts, just the phenotypes are a little more precise leading to slightly increased genetic signals. 5/
December 17, 2024 at 5:44 AM
Likewise, the GWAS of blood count setpoints is almost the same as past GWASs of blood counts, just the phenotypes are a little more precise leading to slightly increased genetic signals. 5/
The extra thing here is the blood counts are measured in terms of "setpoints" (a fancy term for the mean of multiple measurements per individual, excluding outliers) instead of the simple arithmetic mean of all measurements per individuals (which is what we typically do in the UK Biobank). 4/
December 17, 2024 at 5:44 AM
The extra thing here is the blood counts are measured in terms of "setpoints" (a fancy term for the mean of multiple measurements per individual, excluding outliers) instead of the simple arithmetic mean of all measurements per individuals (which is what we typically do in the UK Biobank). 4/