Naslov
Estimating incidence of inborn errors of metabolism from the frequency of variants in general population.

Autori
Mihalek, Ivana ; Bodamer, Olaf

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
American Society of Human Genetics 67thAnnual Meeting

Mjesto i datum
Orlando (FL), Sjedinjene Američke Države, 17.10.2017. - 21.10.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
inborn errors, monogenic genetic disorder, metabolism, ExAC

Sažetak
Inborn errors of metabolism (IEM) constitute a large class of genetic diseases, specific in that many of them are amenable to (nutritional) treatment, especially if detected early. As the first-line screening moves from metabolite to genetic, it opens new possibilities for the number of diseases that can be screened for, which in turn may bring them to the attention of the medical and nutrition industry - the existence of eff ective treatment currently being one of the prerequisites for the IEM to be included in the screening panel. Collecting data about the incidence of the IEM on the national level is a diffi cult process, and not systematically pursued. However, the information about human genetic variation is becoming available (e.g. ExAC database) on the scale that enables us to put a bracket on the expected incidence of all recognized IEMs with monogenic origin. We are collecting that information in a publicly available place (monogenic.org). In this presentation we discuss our current experience in using data integration - modeling of the related protein structure, evolutionary conservation, known disease causing variants, and the genetic variability in the protein coding regions of the genome, stratified across ethnic sub-populations - to put an upper limit on the expected incidence of IEMs. In 75% of the cases for which the information about the IEMs prevalence on the US national level we can make a reasonable prediction on its upper limit. The remaining cases, discussed here, bring to the attention the need to collect the information on a deeper genetic level, perhaps extend the defi nition of some diseases to include polygenic origin, and hopefully motivate the need for fur-ther systematic reporting on the IEMs detected through newborn screening.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Računarstvo, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA