Inference of the Cultural Transmission of Reproductive Success from human genomic data: ABC and machine learning methods

International audienc

Inference of the Cultural Transmission of Reproductive Success from human genomic data: ABC and machine learning methods

International audienceThe Cultural Transmission of Reproductive Success (CTRS) is one of the various cultural processes that can impact human genetic evolution. In this process, individuals from large families have more children on average. Here, we develop and evaluate methods to infer this process from genomic data, using two approaches: (1) Approximate Bayesian computation, which uses summary statistics computed on inferred genealogies from genomic data and (2) deep neural networks, which are directly trained on genomic data. These methods rely on large simulated datasets incorporating varying levels of CTRS. Both competing approaches show a good ability to infer CTRS on genomic data and worth investigating under more complex evolutionary histories

Inference of the Cultural Transmission of Reproductive Success from human genomic data: ABC and machine learning methods

International audienceThe Cultural Transmission of Reproductive Success (CTRS) is one of the various cultural processes that can impact human genetic evolution. In this process, individuals from large families have more children on average. Here, we develop and evaluate methods to infer this process from genomic data, using two approaches: (1) Approximate Bayesian computation, which uses summary statistics computed on inferred genealogies from genomic data and (2) deep neural networks, which are directly trained on genomic data. These methods rely on large simulated datasets incorporating varying levels of CTRS. Both competing approaches show a good ability to infer CTRS on genomic data and worth investigating under more complex evolutionary histories

Severe phenotype in patients with large deletions of NF1

International audienceComplete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients