EichlerLab

Population-scale Long-read Sequencing in the All of Us Research Program The All of Us Research Program (AoU) is a national biobank seeking to enroll one million individuals in the United States to link genomic and biomedical data, including short- and long-read whole-geno...

Check out new AoU collaboration paper: Long-read sequencing of 1027 All of Us participants self-identified as African American discovers new structural variant disease associations: www.medrxiv.org/content/10.1... @uwgenome.bsky.social

07.10.2025 07:14 — 👍 0    🔁 0    💬 0    📌 0

@fkma.bsky.social

Thank you Dr. Danny Miller @danrdanny.bsky.social for hosting, and fantastic job Dr. Mastrorosa @fkma.bsky.social!
@uwgenome.bsky.social

brotmanbaty.org/news/long-re...

25.09.2025 17:19 — 👍 1    🔁 2    💬 0    📌 0

https://pubmed.ncbi.nlm.nih.gov/40848717/

Recent PhD grad Dishuck unveiled NPIP structural variation & evolutionary dynamics across 169 human haplotypes—revealing brain-expressed paralogs & more: pubmed.ncbi.nlm.nih.gov/40848717
🎧 Base by Base Ep 129: Dives into NPIP’s role in our genome: basebybase.castos.com/episodes/str... @hhmi.org

08.09.2025 23:03 — 👍 3    🔁 1    💬 0    📌 0

🧬 How fast do humans mutate?
Our groundbreaking study tracks DNA changes across 4 generations to reveal the pace of human evolution revealing insights into our genetic legacy. Watch now 👉 youtu.be/6TTCZdZd4Y4
#Genetics #Evolution #ScienceVideo #Nature @hhmi.org @uwgenome.bsky.social

08.09.2025 20:56 — 👍 1    🔁 2    💬 0    📌 0

Population differences of chromosome 22q11.2 duplication structure predispose differentially to microdeletion and inversion. The most common genomic disorder, chromosome 22q11.2 microdeletion syndrome (22q11.2DS), is mediated by highly identical and polymorphic segmental duplications (SDs) known as low copy repeats (LCRs; regions A-D) that have been challenging to sequence and characterize. Here, we report the sequence-resolved genomic architecture of 135 chromosome 22q11.2 haplotypes from diverse 1000 Genomes Project samples. We find that more than 90% of the copy number variation is polarized to the most proximal LCR region A (LCRA) where 50 distinct structural configurations are observed (~189 kbp to ~2.15 Mbp or 11-fold length variation). A higher-order SD cassette structure of 105 kbp in length, flanked by 25 kbp long inverted repeats, drives this variation and emerged in the human-chimpanzee ancestral lineage later expanding in humans ~1.0 [0.8-1.2] million years ago. African LCRA haplotypes are significantly longer (p=0.0047) when compared to non-Africans yet are predicted to be more protected against recurrent microdeletions (p=0.00053) due to a preponderance of flanking SDs in an inverted orientation. Conversely, we identified nine distinct inversion polymorphisms, including five recurrent ~2.28 Mbp inversions extending across the critical region (LCRA-D) and four smaller inversions (two LCRA-B, one LCRC-D, and one LCRB-D); 7/9 of these events were identified in haplotypes of African and admixed American ancestry. Finally, we sequence and assemble four families and show that LCRA-D deletion breakpoints map to the 105 kbp repeat unit while inversion breakpoints associate with the 25 kbp repeats adjacent to palindromic AT-rich regions. In one family, we observe evidence of more complex unequal crossover events associated with gene conversion and multiple breakpoints. Our findings suggest that specific haplotype configurations are protective and susceptible to chromosome 22q11.2DS while recurrent large-scale inversions help to explain why this syndrome is less prevalent among individuals of African descent. ### Competing Interest Statement E.E.E. is a scientific advisory board (SAB) member of Variant Bio, Inc. D.P. and J.O.K. have previously disclosed a patent application (no. EP19169090) relevant to Strand-seq. P.M.L. is a founding shareholder of Repeat Diagnostic, Inc. and in Evident Genomics, Inc. He is listed as an inventor in US patent US-20250146052-A1. All other authors declare no competing interests.

www.biorxiv.org/content/10.1...

08.07.2025 18:31 — 👍 0    🔁 0    💬 0    📌 1

https://www.biorxiv.org/content/10.1101/2025.07.04.662981v2

Using >130 human & 12 primate haplotypes, we reconstruct the chromosome 22q11.2 evolution to identify haplotype structures linked to deletions or inversions, explaining the lower prevalence of 22q11.2 deletion syndrome in individuals of African descent. @hhmi.org @uwgenome.bsky.social

08.07.2025 18:30 — 👍 0    🔁 2    💬 1    📌 0

The Eichler lab's new, revamped website is now live! Learn more about the lab's research and scientists @ eichler.gs.washington.edu/

16.05.2025 20:49 — 👍 0    🔁 0    💬 0    📌 0

Our Nature paper (rdcu.be/ei1NM) deep sequencing a 4-generation, 28-member family using multiple sequencing technologies to study transmission of all classes of genetic variation is out! @uwgenome.bsky.social @hhmi.org @pacbio.bsky.social @utah.edu

24.04.2025 00:58 — 👍 12    🔁 3    💬 1    📌 1