Transcript One of the 21st chromosomes completely reattaches to another

Clinical Cytogenetics
Mohamad Nusier M.D., Ph.D.
Clinical Cytogenetics
REVIEW OF MITOSIS AND
MEIOSIS
Rules about chromosomes
 The nuclei of somatic cells contain a fixed number of
chromosomes typical of that particular species
 The chromosomes in the nuclei of somatic cells are
present in pairs
 Cells that contain two similar sets of chromosomes are
called diploid
 One chromosome of each pair is derived from the
maternal parent and the other from the paternal parent

Germ cells (gametes) contain only one set of
chromosomes, consisting of one member of each of the
pairs
 The nuclei of gametes are haploid
 The haploid gametes unite in fertilization to produce the
diploid state of somatic cells
 Mitosis maintains chromosome number while meiosis
halves that number
Cell cycle
Mitosis
 Definition: Nuclear division in which two daughter cells
receive a diploid complement of chromosomes
 Diploid complement of chromosomes in the daughter
cells is identical to that of the parent cell
 Mitosis is accompanied by cytokinesis
 In cytokinesis, the cytoplasm of the cell is divided in half
Mitosis
Overview
Meiosis
 Daughter cells contain only one member of each pair of
chromosomes
 It results in four daughter cells, each genetically different
and each containing one haploid set of chromosomes
 Meiosis consists of two successive rounds of nuclear
division
 In animals, meiosis takes place in meiocytes (primary
oocytes, and spermatocytes)
Crossing over
 Takes place in prophase 1 of meiosis 1.
 Homologous chromosomes find each other in the cell,
interact and pair in a process called synapsis
 During synapsis, chromosomes align themselves along
their entire length (gene for gene)
 Chromosomes exchange pieces of their DNA through a
process called "crossing over"
Crossing over
Clinical cytogenetics
CHROMOSOMAL
ABNORMALITIES
Chromosomal Abnormalities
Abnormalities of Chromosome Number
• Euploid: cell that contains a multiple of 23 chromosomes in its
nucleus, thus haploid gametes and diploid somatic cells are euploid
• Polyploidy: the presence of a complete set of extra chromosomes in a
cell
– Triploidy (69 chromosomes in the nucleus of each cell, karyotype
69,XXX), the most common cause is the fertilization of an egg by
two sperm (dispermy), Meiotic failure
– Tetraploidy (92 chromosomes in each cell nucleus, karyotype
92,XXXX) might be caused by mitotic failure and by the fusion of
two diploid zygotes
• Autosomal Aneuploidy: cells contain missing or additional
chromosomes mostly caused by nondisjunction
– Monosomy: the presence of only one copy of a chromosome in an
otherwise diploid cell
– Trisomy: three copies of a chromosome
• Autosomal monosomies are almost always lethal, but some autosomal
trisomies are compatible with survival
Origin of aneuploids by
non-disjunction at
Meiosis I or II
Origin of aneuploids by
non-disjunction at
Meiosis I or II
Mosaicism
 Presence of two or more
populations of cells with
different genotypes in an
individual who developed
from a single zygote
 May result from mitotic non
disjunction
 May also be the result of
random X chromosome
inactivation in females
Robertsonian translocation between
chromosomes 14 and 21
 Robertsonian translocations
are limited to the acrocentric
chromosomes
 Involves chromosomes 13, 14,
15, 21, and 22
 The long arm (q arm) of one
chromosome will become
attached to the q arm of
another, with the loss of the
two p arms
 Loss of the p arms does not
seem to affect viability
Abnormalities of Chromosome Number
• Trisomy 21:
– Karyotype: 47,XY,+21 or 47,XX,+21
– Causes Down’s syndrome, is the most common autosomal
aneuploidy seen among live births (1 of every 800 to 1000)
– Approximately 95% of Down’s syndrome cases are caused
by non-disjunction, with most of the remainder being caused
by chromosome translocations
– The extra 21st chromosome is contributed by the mother in
approximately 90% of cases
– There is a strong correlation between maternal age and the
risk of producing a child with Down’s syndrome
Down’s syndrome …cont
– Mosaicism is seen in 2% to 4% of Down’s syndrome cases,
and it often accompanies a milder phenotype,
47,XY,+21[10/46,XY[10]
– Some individuals may have tissue specific mosaicism
– Specific genes contributing to the Down’s syndrome
phenotype, DYRK and APP
• The most significant clinical problems are:
– Mental retardation
– Gastrointestinal tract obstruction
– Congenital heart defects
– Respiratory infections
– Leukemia
Down’s syndrome …cont
Down’s syndrome …cont
• One of the 21st
Balanced:
One of the 21st •
chromosomes
• One of the
21st
chromosomes
completely
chromosomes
completely
completely
reattaches
reattaches
to
reattaches
to
to
another
chromosome
another
another
chromosome
chromosome
• Parents known
as
• “carriers”
Parents- known
as
DS
not
Parents known as •
“carriers” - DS not
expressed
“carriers” - DS not
expressed
expressed
Gametes from a 14q, 21q translocation
 Six gametes are possible:
1. translocated 14/21 and normal 14
2. normal 14 and normal 21
3. translocated 14/21 and normal 21
4. normal 21 only
5. normal 14 only
6. translocated 14/21 only
Down’s syndrome …cont
Unbalanced:
• Part of 21st
chromosome is
reattached to another
chromosome
• DS is expressed
Down’s syndrome
Abnormalities of Chromosome Number
• Trisomy 18:
– Karyotype: 47,XY,+18
– Causes Edward’s syndrome
– The second most common autosomal trisomy, 1 per 6000 live
birth
– Approximately 90% of trisomy 18 cases are the result of a
maternal contribution
– Most babies die in the first year and many within the first
month.
Edward’s syndrome
Clenched fist
Edward’s syndrome
Rocker bottom feet
Edward’s syndrome
Abnormalities of Chromosome Number
Trisomy 13:
– Karyotype: 47,XY,+13
– Caused Patau’s syndrome
– About 80% of patients with Patau’s syndrome have full
trisomy 13, most of the remaining patients have trisomy of
the long arm of chromosome 13 due to a translocation
– 50% of these babies die within the first month and very few
survive beyond the first year. There are multiple dysmorphic
features.
– Most cases, as in Down's syndrome, involve maternal nondisjunction.
Patau’s Syndrome
Patau’s Syndrome
Patau’s Syndrome