First complete marmoset genome maps 76 Alzheimer’s-linked genes

Researchers at the University of California, Santa Cruz Genomics Institute have published the first gapless, telomere-to-telomere genome of the common marmoset, a milestone they say will sharpen the study of Alzheimer's disease and other neurodegenerative conditions. The findings, published Thursday in the journal Cell, are part of a broader package of studies from the Telomere-to-Telomere Consortium demonstrating that complete genome assembly is now routine enough to apply across species.biorxiv+1

A New Baseline for Primate Research

The marmoset, a small New World monkey native to South America, has emerged as a leading primate model for neurodegeneration because it naturally develops age-related cognitive decline. But until now, scientists relied on a 2014 reference genome riddled with gaps and unresolved repetitive regions that limited their ability to pinpoint genetic variation accurately.news.ucsc+1

The new assembly, led by UC Santa Cruz Ph.D. student Prajna Hebbar and Professor of Biomolecular Engineering Benedict Paten, adds over 88 megabases of previously unsequenced DNA. Using the reference alongside population data from 230 individual marmosets, the team mapped 76 genes linked to Alzheimer's and Parkinson's disease in humans and found variation patterns that mirror those seen in people.neurosciencenews+3

"We see variation in these marmosets in the same genes that we do in humans, further reinforcing the idea that the marmoset is a good model for studying Alzheimer's disease," Hebbar said.news.ucsc+1

Novel Gene Discoveries

Among the most notable findings, the team identified previously undescribed transcript variants of PSEN1, the gene most frequently implicated in early-onset familial Alzheimer's disease. The researchers also fully resolved the Major Histocompatibility Complex, a dense cluster of immune-system genes tied to autoimmune conditions, and discovered that marmosets shuffle ribosomal DNA arrays between non-homologous chromosomes in sex-specific patterns not previously documented in the species.news.ucsc+1

Toward Personalized Genomics

The marmoset genome is one of several studies released Thursday showing that T2T sequencing — which the consortium first achieved for a human genome in 2022 — can now be scaled to other organisms at lower cost. Researchers say the advance brings medicine closer to an era of affordable individualized genome references.medicalxpress+1

"Routine T2T genomics is making findings easier and more plausible, as we're able to much more easily access these complex regions," Hebbar said. "It's great to be in an era where we're not stuck with the technical problems — we can go into the biology and make discoveries relevant to human health."news.ucsc+1