[2015 Fall Life Sciences & IBB Regular Seminar]
           
             
         ▶Subject: Optimized sequencing leading to new human genetic syndromes involving transcription, translation,and protein degradation
           
         ▶Speaker: Prof. Gholson Lyon (Cold Spring Harbor Laboratory, Human Genetics, Cold Spring)
                   
         ▶Date: 4:00PM/Sept./11(Fri.)/2015
            
         ▶Place: Auditorium(1F), Postech Biotech Center
           
                 *Abctract
               We conduct genomic studies of families in Utah, where there is a founder effect, large families, and good genealogical records. We optimize whole exome sequencing (WES) and whole genome sequencing (WGS) to identify mutations that segregate with various syndromes. We have characterized several new syndromes, including Ogden Syndrome and TAF1 Syndrome. Ogden Syndrome is the first human disorder involving a hypomorphic allele of an enzyme involved in the N-terminal acetylation of proteins, which is a very common protein modification. Ogden syndrome is X-linked, and the affected males harbour a Ser37Pro change in hNaa10, the catalytic subunit of NatA, the major human NAT involved in the co-translational acetylation of proteins. Structural modeling of the human NatA and its S37P mutant highlight differences in regions involved in catalysis and at the interface between hNaa10 and the auxiliary subunit hNaa15. Biochemical data further demonstrate a reduced catalytic capacity and an impaired interaction between hNaa10 S37P and hNaa15 as well as hNaa50 (NatE), another interactor of the NatA complex. N-terminal acetylome analyses revealed a decreased acetylation of only ~30 NatA and NatE substrates in Ogden syndrome cells, supporting the genetic findings and our hypothesis regarding reduced Nt-acetylation of a small subset of NatA/NatE-type substrates as an etiology for Ogden Syndrome. TAF1 Syndrome presents in two brothers with severe intellectual disability and very distinctive facial features. We identified a maternally inherited missense variant in an X-chromosomal gene, TAF1, and a “genotype-first” approach led us to other families with variants in TAF1 and a clinical presentation very similar to the two brothers with TAF1 Syndrome. Extensive functional studies have enabled us get at a more mechanistic understanding for how mutations in these basic processes of transcription and N-terminal acetylation can lead to these distinct syndromes.

                 
        ▶Inquiry: Prof. Cheol-Sang Hwang (279-2352) 
    
           * This seminar will be given in English.
       please refrain from taking photos during seminars. *