Welcome to the Chromosome Anomaly
Collection. This Collection contains examples of
unbalanced chromosome abnormalities (UBCAs)
without phenotypic effect. These are anomalous
in the sense that the great majority of
cytogenetically visible UBCAs do have phenotypic
consequences which would be likely to come to
medical attention. The Collection also includes
the cytogenetically visible euchromatic variants
that can now be regarded as part of the
continuum of copy number variation in the human
genome. A more detailed review has been
published (Barber JCK, J Med Genet, 42, 609-629,
2005). Download review:
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Disclaimer
This Collection is designed to help
Geneticists, Physicians and families by
providing a summary of as many of the known
examples as possible. While every attempt has
been made to accurately replicate details from
publications in full or in abstract, no
responsibility for the accuracy of the
information nor the decisions which might be
made in the light of this Register can be taken
by the compiler who has constructed the attached
Charts.
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Structure of Register
The Collection has been divided into
Unbalanced Chromosome Abnormalitites (UBCAs) and
Euchromatic Variants (EV). UBCAs involve the
addition (duplication) or removal (deletion) of
one of the two copies of each chromosomal
segment present in normal diploid individuals.
The majority of the established EVs involve
variable regions of the genome in which
pseudogene or gene segments are present in
multiple copies that are visible under the light
microscope when copy number is high enough.
The absence of phenotypic consequences can
usually be established only when a parent and
child with the same chromosome abnormality are
both phenotypically normal, or, inferred when an
affected child has an unaffected parent.
Consequently, this Collection is almost entirely
composed of transmitted chromosomal imbalances.
These have been sub-divided into three major
colour coded groups: |
- In Group I, both parents and children
are phenotypically normal. The majority of
these families are ascertained at prenatal
diagnosis. These examples provide precedents
for a normal phenotype associated with
imbalance of a particular region. They
cannot, however, guarantee that all other
examples with the same chromosomal
breakpoints will necessarily be free of
phenotypic consequences. Four This may be
especially true of de novo examples of the
same abnormality. Nevertheless, four
examples without direct transmission have
been included in Group 1 (the dup(9) of
Stumm et al, 2002, the del(10) of Davis et
al, 1999, the dup(13) of Rivera et al, 1981
and the dup(18) of Starke et al, 2001).
- In Group II, the majority of families
are ascertained because of the phenotype of
the proband but parents with the same
chromosome abnormality are unaffected. The
chromosome abnormality may therefore be
considered a coincidental finding. In a
number of cases, however, genomic imprinting
explains the presence or absence of a
phenotype depending on the sex of the
transmitting parent.
- For comparison, Group III contains
directly transmitted chromosome
abnormalities that generally have mild
phenotypic consequences in both parents and
children.
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Accessing the Collection
UBCAs are illustrated on a chart with bars
on the
Idiograms which indicate the location and
extent of each imbalance. Duplications are on
the left hand side and deletions on the right
hand side of each chromosome. Click on the bar
to access the summary chart with further details
and click on the abbreviated reference to obtain
the full reference.
EVs are illustrated with arrows which point to
the approximate location of the expanded
segments in each case. Click on the bar to
access the summary chart with further details
and click on the abbreviated reference to obtain
the full references. |
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| Notes: |
- This Collection concentrates on
unbalanced cytogenetically visible
abnormalities but currently excludes
supernumerary marker chromosomes, ring
chromosomes, submicroscopic abnormalities
only visible by FISH, satellited autosomes
and heterochromatic variants.
- It should be remembered that phenotypic
variability is the hallmark of many
chromosomal and non-chromosomal conditions.
The working conclusions that arise from this
Anomaly Register can be summarised as:
- most visible chromosome
abnormalities have phenotypic
consequences.
- exceptions to this rule exist but
are frequently unique to a single
family.
- only by gathering further examples
will it be possible to identify regions
of the genome that are consistently free
of phenotypic consequences.
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Contribute data:
Genetic centres are invited to submit
additional examples may make it possible to
establish whether the phenotypically normal
abnormality carriers represent the benign end of
a spectrum of phenotypic effect, or, whether
there are indeed cytogenetic abnormalities that
are consistently free of phenotypic
consequences. A Chromosome Anomaly Collection
Submission Form
is available here or from the compiler. |
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Links:
Other sources of useful information about
chromosome abnormalities and variants can be
found in the
Borgaonkar Online Database or as hard copy
in: |
- Borgaonkar DS (1997) Chromosomal
variation in man; a catalogue of chromosomal
variants and anomalies. 8th ed, Wiley, ISBN
0-471-24332-9
- Schinzel A (2001) Catalogue of
unbalanced chromosome aberration in man. 2nd
ed, de Gruyter, ISBN 3-11-011607-3
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| Other databases that may overlap with the
CAC include: |
- The European Cytogenetic Association
Register of Unbalanced Chromosome
Abnormalities which allows on-line
registration and to collection of large
numbers of rare cytogenetic and molecular
cytogenetic aberrations at
www.ecaruca.net/.
- The DatabasE of Chromosomal Imbalance
and Phenotype in Humans using Ensemble
Resources (DECIPHER) which has been inspired
by the need to distinguish clinically
significant imbalances from transmitted
imbalances or polymorphisms detected using
micro-arrays. On-line registration and
submission can be carried out at
www.sanger.ac.uk/PostGenomics/decipher
- The unprecedented degree of large scale
copy number variation found with array
techniques is also being gathered in the
Structural Variation Database and the
Database of Genomic Variants
- The long established UK Association of
Clinical Cytogeneticists (ACC)
Chromosome Abnormality Database (CAD) is
also now on-line for registration and free
searches
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| This Collection has been compiled by Dr John
Barber who can be contacted at: |
National Genetics Reference Laboratory
(Wessex)
Salisbury District Hospital
Salisbury
SP2 8BJ
Tel: +44 (0)1722 429080
Fax: +44 (0)1722 338095
e-mail:
john.barber@salisbury.nhs.uk |
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| Acknowledgement |
| The help of Gemma Potts, Carolyn Wallis,
Kelley Gardner and Mac Gardner in the
construction of this entry is gratefully
acknowledged. Viv Maloney kindly constructed the
chromosomal idiograms. |
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