UC Davis Identifies Genes Linked to Brain Size and Synapse Signalling

Researchers at UC Davis, alongside collaborators from Washington University St. Louis, the National Human Genome Research Institute, and University College London, have identified two genes – GPR89B and FRMPD2B – linked to human brain features using the recently completed telomere-to-telomere human genome. The study, published on July 21 in Cell, filtered approximately 250 candidate gene families to reveal that GPR89B correlates with slightly larger brain size, while FRMPD2B is linked to altered synapse signalling. This work, funded by the National Institutes of Health, National Science Foundation and The Wellcome Trust, provides a resource for investigating potential genetic links to conditions including language deficits and autism.

Unlocking the Duplicated Genome

The study identified approximately 250 candidate gene families through a filtering process based on three criteria: expression within the brain, presence in all humans as determined by data from the 1000 Genomes Project, and a low degree of variation among individuals. Subsequent investigation utilising the zebrafish as an animal model revealed that at least two of these genes may contribute to specific human brain features, providing potential insights into human brain evolution. The gene GPR89B demonstrated a correlation with slightly larger brain size, while FRMPD2B was linked to altered synapse signalling.

The resulting dataset, published in Cell, is intended to serve as a resource for the wider scientific community, facilitating the screening of duplicated genomic regions for mutations potentially linked to conditions such as language deficits or autism. These mutations may have been previously undetected in genome-wide studies, offering new avenues for investigation into the biological basis of these conditions. This research opens up previously unexplored genomic territory, potentially furthering understanding of human brain evolution and associated neurological conditions.

Identifying Genes Linked to Brain Development

Historically, identifying genes within duplicated regions of the genome presented a significant problem for researchers, often leaving them uncertain where to begin. The recent completion of the telomere-to-telomere human genome – a complete sequence including previously omitted difficult regions – has provided a crucial resource for new discoveries in these areas, building upon the first draft published in 2001. DNA repeats are thought to be important for evolution, as they can generate new versions of existing genes upon which natural selection can act, suggesting their role in the trajectory of human brain evolution.

The research team, including members from UC Davis, Washington University St. Louis, the National Human Genome Research Institute, and University College London, utilised this complete human genome to identify duplicated genes. This process involved filtering candidates based on brain expression, consistent presence across humans (utilising data from the 1000 Genomes Project), and a low degree of variation among individuals, ultimately yielding approximately 250 candidate gene families. The resulting dataset, published in Cell, is intended as a resource for the wider scientific community, facilitating the screening of duplicated regions for mutations potentially linked to conditions such as language deficits or autism.

A Resource for Neurological Research

The research detailed in Cell provides a resource intended for wider scientific use, facilitating the screening of duplicated regions for mutations potentially linked to conditions such as language deficits or autism – mutations that may have been missed in previous genome-wide studies. This work builds upon the completion of the telomere-to-telomere human genome, a complete sequence including previously omitted difficult regions, and the first draft published in 2001.

The study was conducted by a collaborative team including researchers from UC Davis, Washington University St. Louis, the National Human Genome Research Institute, and University College London. Funding for the research was received from the National Institutes of Health, the National Science Foundation, and The Wellcome Trust.