Genetic test results Why did this happen and can it happen again?

A clinical geneticist or genetic counsellor will explain which Deletions can be inherited from an unaffected or affected
piece (or pieces) of genetic material is missing. The parent, or happen as a new event ( de novo ).
information given will include the location and size of the Chromosome sections can be lost during the formation of
deletion as well as the known significance of any genes eggs or sperm or during the complicated replication
included in the change, and whether the same or a similar process that is needed to produce new cells as we grow
change has been seen before in another person. and develop. Sometimes similar deletions occur in many
Chromosomal deletions are commonly identified using a unrelated people due to regions of repetitive DNA. It is
genetic test called microarray analysis (such as array CGH). important to know that nothing could have been done to
The results of this test are likely to read something like the prevent the deletion from happening. It was a natural event
following example: that no lifestyle, dietary or environmental factors are
known to cause. There is nothing that anyone did before,
arr[hg19] 16p11.2 (29653028-30190538)x1 dn during or after pregnancy to cause the deletion.
arr The analysis used microarray technology If a child has inherited the deletion, the chances of having
hg19 This is the reference DNA sequence another child with the same deletion is about 50%. If the
that the base pair numbers refer to, deletion is de novo, the chances are estimated at less than
in this case human genome build 19 1%. Your genetics centre should be able to offer
16p11.2 The test revealed a DNA change on the counselling to all family members, including individuals
p arm of chromosome 16 in band 11.2 with the deletion or microdeletion, regarding the chances
(29653028-30190538) The DNA change is identified of having a(nother) child with the same change.
by its base pair numbers (the points where the
chromosomal change has occurred).
In this example, the DNA change lies between
Inform Network Support Deletions and
Rare Chromosome Disorder Support Group,

x1
base pairs (bp) 29653028 and 30190538.
This region covers 537,510 base pairs (≈0.5 Mb)
There is 1 copy of the piece of DNA specified.
The Stables, Station Road West,
Oxted, Surrey. RH8 9EE. UK.
Tel +44(0)1883 723356
microdeletions
Since there should be 2 copies of chromosome 16, info@rarechromo.org
this indicates that the DNA change is a deletion www.rarechromo.org
dn The deletion occurred de novo (as a ‘new event’). Join Unique for family links, information and support.
The parents’ chromosomes have been checked Unique is a charity without government funding, existing entirely on
and no deletion has been found in this region donations and grants. If you can, please make a donation via our
website at www.rarechromo.org/donate Please help us to help you!
of chromosome 16
This information guide is not a substitute for personal medical
If a deletion in a person is identified as de novo, it is very advice. Families should consult a medically qualified clinician in all
unlikely to occur in any siblings of that person. If a test matters relating to genetic diagnosis, management and health.
result is followed by mat, the deletion has been inherited Information on genetic changes is a very fast-moving field and while
from the mother (maternal); if it is followed by pat, the the information in this guide is believed to be the best available at
the time of publication, some facts may later change. Unique does
deletion has been inherited from the father (paternal).
its best to keep abreast of changing information and to review its
Genetic test results may also contain a list of morbid genes. published guides as needed. This booklet was compiled by Unique
These are genes known to cause symptoms if they do not (AP) and reviewed by Dr. Gregory Costain, Division of Clinical and
Metabolic Genetics, The Hospital for Sick Children, Toronto,
function as expected. Some morbid genes only cause
Canada.
symptoms if there are no functional copies, while others Version 1 (AP)
are "dose-sensitive" (may cause symptoms if there are Copyright © Unique 2020
usually two copies and one is lost or altered) or
"imprinted" (one copy is already switched off). Rare Chromosome Disorder Support Group Charity Number 1110661 rarechromo.org
Registered in England and Wales Company Number 5460413
 What are deletions and microdeletions? Deletion location What’s in a deletion?
A chromosomal deletion is the loss of a piece of genetic Chromosomal deletions are often described by their Chromosomes are made from incredibly long pieces of
material from a chromosome. Deletions can vary in size location on a specific chromosome; which ‘arm’ they are tightly packaged DNA (deoxyribonucleic acid). DNA exists as
and those that are too small to be seen under the on and which ‘band’ they are in. a double stranded structure (called a double helix, as shown
microscope are sometimes called microdeletions. What are chromosome arms? in the image below).
Each chromosome consists of two ‘arms’ joined together A single strand of DNA is made from
What are chromosomes? building blocks called nucleotides, each
at a constricted part of the chromosome called the
centromere . The shorter arm is called the ‘p’ arm, and containing one of four bases: G (guanine),
Our bodies are made up of many different types of cells, base
the longer arm is known as the ‘q’ arm. pairs A (adenine), T (thymine), or C (cytosine).
most of which contain our chromosomes. Chromosomes Two strands of DNA coil around each other
come in pairs; one member of each pair is usually inherited p arm q arm and are held together by bonds between
from each parent. Most cells have 23 pairs of chromosomes DNA
strand the base pairs A and T or G and C.
(a total of 46). Eggs and sperm, however, have a single copy
DNA can be thought of as a sequence of letters (bases) but
of each chromosome pair; when a sperm fertilises an egg at
unlike an alphabet, the sequence only uses 4 letters
conception, the number of chromosomes is restored to 46.
telomere centromere telomere (G, A, T, C). Within these long sequences of DNA, there are
We usually have 22 chromosome pairs called autosomes, regions that code for our genes, which are the ‘instructions’
numbered 1-22 roughly according to decreasing size, The tips of the arms are called telomeres. If a piece of
that our bodies use to function, grow and develop. We have
and two sex chromosomes that determine the chromosome is missing from the tip of a chromosome it’s
over 20,000 genes and each one has a distinct role in different
characteristics associated with biological sex. Males usually called a terminal deletion. If a piece of chromosome is
parts of the body at different stages of development.
have one X and one Y chromosome (XY), and females usually missing from within one of the arms, it’s called an
interstitial deletion; those closer to the centromere are Due to advances in genetic technologies, pieces of missing
have two X chromosomes (XX).
called proximal deletions, those closer to the arm tips are DNA can now be easily identified, together with their size,
Chromosomes can’t location and most importantly, gene content. When we try to
be seen with the called distal deletions.
assess what possible effects a deletion may have, we look at
naked eye but if cells What are chromosome bands? which genes (or sequences of DNA that control the activity of
are prepared in a Each of our chromosomes can be identified as a series of genes) are affected.
specific way, the bands visualised by specific laboratory staining
chromosomes can be techniques. The bands on each chromosome arm are Deletion size
stained and viewed numbered starting at the centromere (which has been
under a microscope. assigned the number 10) and finishing at the telomere. The size of a deletion is measured in bases or base pairs (bp).
This image shows the
Deletions are described by their band location on a The first base pair of each chromosome is at the tip
chromosomes present
chromosome arm. Descriptions start with the number of (telomere) of the p arm, and the last is at the tip of the q arm.
in a typical male (XY)
the chromosome e.g. chromosome 20 (as shown in the Since DNA sequences are so long, they are often measured
cell. Chromosomes pairs 1-22, X and Y (male) image below), followed by the arm letter, p or q. The in megabases (Mb’s; 1 Mb = 1 million bp) or kilobases (kb’s;
number of the region e.g. 1 is then noted, followed by the 1 kb =1000 bp). Deletions smaller than 5 Mb (that’s 5,000,000
How will a deletion affect me or my child? band number e.g. 3, then any smaller sub-bands such base pairs) are sometimes known as microdeletions.
as .2 or an even smaller division of a sub-band e.g. .33. Deletions can vary in size from one base pair (known as a
Effects of chromosomal deletions vary greatly between p arm q arm
sequence variant) to an entire chromosome (known as
individuals and are dependent on which chromosome is monosomy). But the majority of deletions currently identified
affected and what genetic material is missing. Deletions can Chromosome using standard technologies are between a few hundred kb
20
affect intellectual abilities, and/or cause physical and and a few Mb. Such deletions are commonly known as copy
functional changes to our bodies. Deletions thought to cause number variants (CNVs) since the usual copy number of the
symptoms are called pathogenic, those that are thought to piece of deleted DNA has been reduced by one. For
20p11.23
20p11.22
20p11.21

20q11.21
20q11.22
20q11.23

20q13.11
20q13.12
20q13.13

20q13.31
20q13.32
20q13.33
20p12.3
20p12.2
20p12.1

20p11.1
20q11.1

20q13.2

have no ill effect are called benign. There are also many Band autosomal chromosomes (1-22) this means the expected
20p13

20q12

deletions of uncertain significance that may be reclassified copy number of two (one from each chromosome pair), has
as benign or pathogenic when we’ve learnt more about them. been reduced to one, due to the deletion.