RESUMO
The risk of Hirschsprung disease (HSCR) is â¼15/100 000 live births per newborn but has been reported to show significant inter-individual variation from the effects of seven common susceptibility alleles at the RET, SEMA3 and NRG1 loci. We show, by analyses of these variants in 997 samples from 376 HSCR families of European ancestry, that significant genetic risk can only be detected at RET (rs2435357 and rs2506030) and at SEMA3 (rs11766001), but not at NRG1. RET rs2435357 also showed significant frequency differences by gender, segment length of aganglionosis and familiality. Further, in combination, disease risk varied >30-fold between individuals with none and up to 6 susceptibility alleles. Thus, these polymorphisms can be used to stratify the newborn population into distinct phenotypic classes with defined risks to understand HSCR etiology.
Assuntos
Doença de Hirschsprung/genética , Neuregulina-1/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas c-ret/genética , Semaforina-3A/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , População Branca/genéticaRESUMO
In this article, we show how relativistic α-stable processes can be used to explain quasiballistic heat conduction in semiconductors. This is a method that can fit experimental results of ultrafast laser heating in alloys. It also provides a connection to a rich literature on the Feynman-Kac formalism and random processes that transition from a stable Lévy process on short time and length scales to the Brownian motion at larger scales. This transition was captured by a heuristic truncated Lévy distribution in earlier papers. The rigorous Feynman-Kac approach is used to derive sharp bounds for the transition kernel. Future directions are briefly discussed.