knowledge transfer in the post-genome world: keeping up is not good enough timothy d. smith
TRANSCRIPT
![Page 1: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/1.jpg)
Knowledge Transfer in thePost-Genome World:
keeping up is not good enoughTimothy D. Smith
![Page 2: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/2.jpg)
Rebholz-Schuhmann et al. 2005
![Page 3: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/3.jpg)
Jensen et al. 2006
![Page 4: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/4.jpg)
![Page 5: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/5.jpg)
![Page 6: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/6.jpg)
We analysed the TGM2 gene in 205 patients with clinically
defined Maturity Onset Diabetes of the Young (MODY) or
early-onset type 2 diabetes. We found two novel heterozygous
mutations (c.989T>G, p.M330R; c.992T>A, p.I331N), which
were not detected in 300 normoglycemic controls. All
mutations were in residues which are located close to the
catalytic site and impaired transamidating activity in vitro.
Gene expression of TGM family genes and localization of TG2
in normal human pancreas indicated that TG2 is the only
transglutaminase significantly expressed in human pancreatic
islet cells. We conclude that reduced TG2 activity can
contribute to disorders of glucose metabolism possibly via an
impairment of insulin secretion.Porzio et al. 2007
![Page 7: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/7.jpg)
SPECIES human
GENE NAME TGM2
ACCESSION NM_198951
VARIANT c.989T>G
BASE CHANGE TYPE Substitution
PROTEIN EFFECT -
PHENOTYPE Impaired enzyme activity; glucose metabolism disorder
![Page 8: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/8.jpg)
CDC28
Cyclin-dependant kinase 1
Cdk1
![Page 9: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/9.jpg)
hairy
![Page 10: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/10.jpg)
white
![Page 11: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/11.jpg)
T98G
L23A
![Page 12: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/12.jpg)
The mutation in exon 7 c.989T>G (p.M330R), was
found in a Danish patient (D79) with early onset type
2 diabetes. Porzio et al. 2007
![Page 13: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/13.jpg)
c.989T>G
![Page 14: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/14.jpg)
TGM2:c.989T>G
![Page 15: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/15.jpg)
...the substitution of a nucelotide at position 989 to
guanine...
![Page 16: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/16.jpg)
A second heterozygous mutation in exon 7 c.992T>A
(p.I331N) was identified in a French family (F193, Fig. 1B).
The mutation was detected in the index case (Fig. 1B, II-2),
who presented with diabetes at the age of 39 (therapy: diet)
and in two diabetic siblings (II-4, II-6, treated with diet and
OHA, respectively).
![Page 17: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/17.jpg)
Solutions
![Page 18: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/18.jpg)
![Page 19: Knowledge Transfer in the Post-Genome World: keeping up is not good enough Timothy D. Smith](https://reader035.vdocument.in/reader035/viewer/2022070306/5519229755034642428b4bb8/html5/thumbnails/19.jpg)
Knowledge Transfer in thePost-Genome World:
keeping up is not good enoughTimothy D. Smith