Page 138 - ASHG 2013 Program Guide

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Saturday, October 26
Concurrent Invited Session III (70-76)
SESSION 71 – More or Less: Copy Number Variation
and Human Adaptation
Room 258, Level 2, Convention Center
Chack-Yung Yu, The Ohio State Univ; Ed J.
Hollox, Univ. of Leicester
Inter-individual copy number variation (CNV) of
genomic DNA sequences is an important mechanism
that drives the diversity of phenotypes and contributes
to differential disease susceptibilities. The role of gene
loss and gene gain in evolution has been discussed
for many years. However, only recently have studies
shown that continuous gain or loss of DNA sequences
have played an important role in the speciation of
humans and other primates, and of adaptation within
a species to different environments. Phenotypes
involved include human-specific brain morphology,
the lack of a penile spline in men, and variation in
resistance to infectious disease between populations.
Genetic mechanisms include duplication and
divergence of coding DNA sequences, and deletion
of regulatory DNA sequences. Scientific approaches
range from detailed structural and functional
characterization of single loci to genomewide
overviews across multiple species. In this session,
we will present an overview of the latest research,
demonstrating the long strides that have been made
in linking the evolution of phenotype to molecular
changes in the genome.
Evolution of segmental duplications and
novel neural genes.
E. E. Eichler. Howard Hughes
Med. Inst. and Univ. of Washington.
Human-specific loss of regulatory DNA
and the evolution of human-specific traits.
D. M.
Kingsley. Howard Hughes Inst. and Stanford Univ.
Sch. of Med.
Primate structural genomic variation
evolving under positive selection.
C. Lee. Brigham
and Women’s Hosp.
Structural variation of beta-defensins:
Welcome to the dynamic genome.
E. J. Hollox. Univ.
of Leicester, U.K.
Saturday, October 26
Concurrent Invited Session III (70-76)
SESSION 72 – Somatic Mutations in Human Disease —
Piecing Together the Mosaic
Room 210, Level 2, Convention Center
Leslie Biesecker, NHGRI/NIH; William
Dobyns, Univ. of Washington
Our field is dominated by three genetic disease
concepts’ ‘simple’ Mendelian disorders, complex
disorders, and the complex somatic genetics of
cancer. Recently, a new model is coming to the
fore, that of the simple mosaic disorder – disorders
caused by mosaicism for a mutation in a single gene.
This model is on the rise because recent genomic
techniques have improved detection of genomic
alterations in mosaic tissues. These developments are
accelerating the discovery of a wide array of human
disease that is attributable to mosaic mutations. While
it has long been known that gonadal mosaicism can
explain recurrence of dominant disorders and that
cancer is a complex mosaic genomic disease, only
now are we beginning to appreciate the breadth and
frequency of mosaic disorders. While the mosaic
disorders of dermatologic disorders and overgrowth
are most readily recognizable, mosaicism can affect
any tissue and may explain a substantial fraction
of human disease. The session will begin with the
phenotypes of mosaic disorders, emphasizing
dermatologic disorders to set the clinical context for
the session. Second will be a review of the molecular
genetics of mosaic cytogenetic and copy number
variation, as elucidated initially by microscopic and
now SNP array analysis. Third will be an overview of
the disorders caused by mosaic point mutations in
genes and we will close with a presentation on how
lessons from cancer relate to simple mosaicism. These
presentations will provide the participants with a broad
overview and understanding of the role of somatic
variation in human disease.
The clinical manifestations of mosaicism.
R. Happle. Freiburg Univ. Med. Ctr., Germany.
Cytogenetics and the historical context
of mosaicism.
N. Spinner. Univ. of Pennsylvania.
Single gene mutations and mosaic
genetic disease.
L. Biesecker. NHGRI/NIH.
The mosaic landscape of cancer.
E. ­Mardis. Washington Univ. Sch. of Med.