High resolution gene expression studies in early human development

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High resolution gene expression studies in early
human development
Steve Lisgo, Susan Lindsay Tom Strachan
Institute of Human Genetics (IHG), International
Centre for Life, University of Newcastle, UK
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International Centre for Life, Newcastle
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Studying Early Human Development
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Justification for human studies poorly
conserved genes
Poorly conserved
Absent in mice and other rodents
(but a locus for certain idiopathic short
stature syndromes)
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Some human genes do not have orthologues in mouse
SHOX
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SHOX phenotypes
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SHOX expression in a lateral sagittal section at
CS16
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Testing for human-mouse differences in expression
of highly conserved genes
NOT significant
Significant
Significant
NOT significant
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Human-mouse differences in gene expression
domains for conserved and disease genes
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Human-mouse differences in Wnt7a expression in
the developing midbrain
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WNT7A expression in the developing midbrain and
forebrain
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Calpain-3 expression in the developing mouse
lens and paraxial muscles
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Lens- specific
X
X
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Very few centres worldwide are engaged in
collection of human embryos with ethical
safeguards.
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Newcastle Human Embryo Collection
1st trimester (social termination)
maternal consent ethical committee government
guidelines
karyotype analysis morphological assessment
undamaged
150/year
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Number of embryos according to Carnegie stage
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Number of intact embryos
according to Carnegie stage
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Quarterly collection of intact embryos
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Priorities for gene expression studies in early
human development
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EurExpress strategy human genes
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A breakdown of the genes examined in in situ
hybridisation studies.
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Progress to date
Disease genes on Xq28
Disease genes on Xq
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Monthly output of new genes studied
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5
4
3
2
1
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TBX22 expression during
secondary palate formation
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TBX22 expression during formation of
other craniofacial
structures
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Result Archiving
Initially, large regions painted to a sagittal
section to enable quick mapping
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(No Transcript)
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Towards an electronic database of the developing
human brain
Tom Strachan, Susan Lindsay
Richard Baldock, Duncan Davidson
3D reconstruction
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Optical Projection Tomography Reconstruction of
a CS14 Embryo
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Future plans
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Acknowledgments
Steve Robson Mark Clement-Jones Phil Bullen