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:
transmitted review jmg.pdf (603.9KB)
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 Collection
can be taken by the compiler who has constructed the attached
Structure of Register
The Collection has been divided into Unbalanced Chromosome
Abnormalitites (UBCAs) and Euchromatic Variants (EVs). 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
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.
This may be especially true of de novo examples of the
same abnormality. Nevertheless, five examples without
direct transmission have been added to Group 1
including the dup(9) of Stumm
et al (2002), the del(10) of Davis et al (1999), the dup(11)
of Zarate et al (2007), the dup(13) of Rivera et al (1981)
and the dup(18) of Starke et
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.
Group III, for comparison, are directly
transmitted chromosome abnormalities that generally have mild
in both parents and children.
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 arrow to access the summary
chart with further details and click on the abbreviated reference to obtain
the full references.
Unbalanced chromosome abnormality (UBCA)
Euchromatic Variant (EV) Chart
concentrates on unbalanced cytogenetically visible abnormalities
but currently excludes supernumerary marker chromosomes, ring
chromosomes and heterochromatic variants.
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
1. most visible
chromosome abnormalities have phenotypic consequences.
to this rule exist but are frequently unique to a single family.
3. only by
gathering further examples will it be possible to identify
regions of the genome that are consistently free of phenotypic
Genetic centres are invited to submit additional examples
that 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.
Other sources of useful information about chromosome abnormalities
and variants can be found in the Borgaonkar
Online Database or as hard copy in:
A (2001) Catalogue of unbalanced chromosome aberration in
man. 2nd ed, de Gruyter, ISBN 3-11-011607-3
DS (1997) Chromosomal variation in man; a catalogue of chromosomal
variants and anomalies. 8th ed, Wiley, ISBN 0-471-24332-9
databases that may overlap with the Chromosome Anomaly Collection
Cytogenetic Association Register of Unbalanced Chromosome Abnormalities
(ECARUCA) which contains details of thousands of published
cytogenetic imbalances and is prospectively gathering rare
cytogenetic and molecular cytogenetic aberrations. On-line
registration and submission can be carried out at www.ecaruca.net/.
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.
degree of large scale copy number variation found with array
techniques is also being gathered in:
1. the Database
of Genomic Variants (http://projects.tcag.ca/variation/)
2. the Structural
Variation Database (http://humanparalogy.gs.washington.edu/structuralvariation/).
The long established
UK Association of Clinical Cytogeneticists (ACC) Chromosome Abnormality Database (CAD) is
also now on-line for registration and free searches
Collection has been compiled by Dr John Barber who can be contacted
Genetics Reference Laboratory (Wessex)
Salisbury NHS Foundation Trust
Tel: +44 (0)1722 429080
Fax: +44 (0)1722 338095
help of Gemma Watkins, Carolyn Wallis, Kelley Gardner and Mac
Gardner in the construction of this entry is gratefully acknowledged.
Viv Maloney kindly constructed the chromosomal idiograms.