Next generation sequencing technologies for rare Mendelian disorders striking potential and ongoing challenges外文资料.pdfVIP

Molecular and Cellular Probes 29 (2015) 259 Contents lists available at ScienceDirect Molecular and Cellular Probes journal homepage: /locate/ymcpr Next generation sequencing technologies for rare Mendelian disorders: striking potential and ongoing challenges Diseases are considered as rare (“orphan”) disorders if they brainstem and spinal cord involvement (Koehler et al.) or identi?ed occur with a frequency of <1:2000 in the general population. How- novel mutations for severe encephalopathy (Granzow et al.) and a ever, they are only rare if regarded individually: altogether >7000 connective tissue disorder with overlap to Marfan and Loeys- such diseases are known to date (giving a cumulative prevalence Dietz syndromes (Kuechler et al.). of 6e8% [1]) which not only pose individual problems and suffering However, we also have to be aware of the problems and down- for the affected families but also collectively represent a consider- falls of the novel NGS techniques. First of all, for exome- or even able burden for modern health care systems [2]. The majority of genome-wide approaches the geneticist has to rely on software rare disorders is caused by monogenic inheritance, but since there tools which help to sort the huge amount of data for the relevant are mostly only few affected families for a given disease, the iden- mutation(s). As illustrated in the paper by Granzow et al., different ti?cation of the disease-causing gene(s) has not been achieved in ?ltering of the same data may give quite diverging results, so that many cases until recently. interpretation of the data must still be regarded cautiously. Further,