Chromosomal Abnormalities ISDK

October 13, 2012

A chromosome abnormality reflects an abnormality of chromosome number or structure. We can classify them into:

I- NUMERICAL ABNORMALITIES

II- STRUCTURAL ABNORMALITIES

What are chromosome abnormalities?Chromosomal Abnormalities

The majority of human chromosomal abnormalities occur in the Autosomes. 

Most of these abnormalities are monosomies or trisomies.  In the case of a monosomy, there is only one copy of each kind of

chromosome instead of the usual pair of homologous chromosomes.  With trisomy, there are three of each type of chromosome. 

All fetuses with autosomal monosomies spontaneously abort early in pregnancy. 

Likewise, almost all fetuses with trisomies die before birth.  Those that survive usually have multiple physical

malformations, mental retardation, and relatively short lives.

Characteristics of Chromosomal Abnormalities

I. NUMERICAL ABNORMALITIES

Chromosomal abnormalities in the number of chormosomes.

1.Euploidy: Cells has chromosomes multiple of 23 such as

– 23, 46. 69, and 92

These may be normal or AbnormalNormal– Haploid cells : Gametes has 1 copy each 23 cells– Diploid cells: Somatic cells has 2 copy each 23 x2 46

NUMERICAL ABNORMALITIESHOW DOES IT HAPPEN

Abnormal Tripoloidy 3 copies of each chromosome 23 x 3= 69

1 egg fertilized by 2 sperms

Tetra ploidy. 4 copies of each chromosome 23 x 4= 69

1 egg fertilized by 3 sperms

Deviation from normal number of chromosomes due to loss or gain of specific chromosomes.

Generally caused by non disjunction of chromosome during meiosis.

is one extra (trisomy ; 2n + 1 ) or one less chromosome (monosomy ; 2n - 1).

It is a major cause of human reproductive failure. Most human miscarriages are aneuploids.All autosomal monosomies are lethelAll Trisomies are also lethelBut some Trisomies[ three copies of a particular

chromosomes] are compatible with survival to term with chromosomes 13, 18, and 21.

2.Aneuploidy

Non Disjunction

Non Disjunction

Autosomal Chromosome Problems

The result of an extra copy of chromosome 21. People with Down syndrome are 47, 21+.

Down syndrome affects 1:700 children and alters the child's phenotype either moderately or severely:

characteristic facial features, short stature; heart defects

susceptibility to respiratory disease, shorter lifespan

often sexually underdeveloped and sterile, usually some degree of mental retardation.

Down Syndrome is correlated with age of mother but can also be the result of nondisjunction of the father's chromosome 21.

Down Syndrome (Trisomy 21)

Down Syndrome (Trisomy 21)

Patau syndrome (Trisomy 13) Serious eye, brain, circulatory defects as well as cleft

palate. 1:5000 live births. Children rarely live more than a few months.

Patau syndrome (Trisomy 13)

Edwards Syndrome (Trisomy 18)

• Almost every organ system affected 1:10,000 live births. Children with full Trisomy 18 generally do not live more than a few months.

DiGeorge syndrome(Monosomy 22)22q11.2 deletion syndrome

• Congenital thymic aplasia, and thymic hypoplasia

• Is a syndrome caused by the deletion of a small piece of chromosome 22.

• The deletion occurs near the middle of the chromosome at a location designated q11.2

• Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems

DiGeorge syndrome

Precursor T cell differentiation defect Lack of T helper (Th) cells , Cytotoxic T cells (CTL) and

T regulatory (Treg) cells B cells are present but T-dependent B cell responses are

defective Anti-viral and anti-fungal immunity impaired Developmental defect in the 3rd and 4th pharyngeal pouch Results in facial defect and congenital heart disease Treated with thymic transplant Autosomal dominant trait

Which of the following is an example of monosomy?

A. 46,XXB. 47,XXXC. 69,XYYD. 45,X

Sex Chromosome(X Y) Abnormalities Male Sex Female Sex

X Chromosome

Y Chromosome

The majority of known types of chromosomal abnormalities involve Sex chromosomes.

In frequency of occurrence, they are only slightly less common than autosomal abnormalities. 

However, they are usually much less severe in their effects. 

Sex chromosome abnormalities are gender specific. 

Sex Chromosome Abnormalities

Male Sex 1. Klinefelter Syndrome

Klinefelter syndrome: males inherit one or more extra X

chromosomes--their genotype is XXY. 

They characteristically have relatively high-pitched voices,

asexual to feminine body contours as well as breast

enlargement, and comparatively little facial and body hair. 

They are sterile or nearly so, and their Testes and Prostat

glamds are small.  As a result, they produce relatively small

amounts of testosterone.

Male Sex 1. Klinefelter Syndrome

XYY syndrome males inherit an extra Y chromosome, their genotype is XYY. 

As adults, these "super-males" are usually tall (above 6 feet) and generally appear and act normal. 

However, they produce high levels of testosterone.  During adolescence, they often are slender, have

severe facial acne, and are poorly coordinated.  They are usually fertile and lead ordinary lives as

adults. 

2. XYY Syndrome

2. XYY Syndrome

Female Sex 1. Turner syndrome

Turner syndrome occurs when females inherit only one X chromosome--their genotype is X0.

  If they survive to birth, these girls have abnormal growth patterns. 

They are short in stature, averaging 4 foot 7 inches as adults, and often have distinctive webbed necks (i.e., extra folds of skin), small jaws, and high arched palates. 

They generally lack prominent female secondary sexual characteristics.  They have exceptionally small, widely spaced breasts, broad shield-shaped chests, and turned-out elbows. 

Their ovaries do not develop normally and they do not ovulate. 

Female Sex 1. Turner syndrome

Female Sex 1. Turner syndrome

Inherit three X chromosomes--their genotype is XXX or more rarely XXXX or XXXXX.  As adults, these "super-females" are usually an inch or so taller than average with unusually long legs, but otherwise appear normal. 

They have normal development of sexual characteristics and are fertile.  They may have slight learning difficulties and are usually in the low range of normal intelligence (especially the XXXX and XXXXX individuals). 

2. Triple-X females

Sex Chromosome Abnormalities

Female Genotype Syndrome Male

Genotype Syndrome

XX normal XY normal

XO Turner  XXY Klinefelter

XXX Triple-X XYY XYY

Mosaicism and Chimerism

Mosaics and chimeras are persons that have more than one genetically-distinct population of cells.

In mosaics, the genetically different cell types all arise from a single zygote.

In chimeras originate from more than one zygote.

Chromosome instability syndromes

They are a group of inherited conditions associated with chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.

The following chromosome instability syndromes are known:

- Ataxia Telagiectasia- Bloom Syndrome- Fanconi Anaemia

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