chromosomal abnormalities a review

Chromosomal abnormalities - A review

Abstract

With the discovery in 1956 that the correct chromosome number in humans is 46, the new era of clinical cytogenetics began its rapid growth. During the next few years, several major chromosomal syndromes with altered numbers of chromosomes were reported, i.e. Downsyndrome (trisomy21), turner syndrome (45,x) and klinefelter syndrome (47,xxy). Since then it has been well established that chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual developmentmental retardation and pathogenesis of malignancy.specific chromosome abnormalities have been associated with over 60 identifiable syndromes. They are present in at least 50% of spontaneous abortions, 6% of stillbirths, about 5% of couples with two or more miscarriages and approximately 0.5% of newborns. In women aged 35 or over, chromosome abnormalities are detected in about 2% of all pregnancies. Some of the abnormalities and their clinical consequences will be Discussed in the following sections.

Key Words: Chromosomal abnormalities, numerical, structural abnormalities, syndromes.

Address for Correspondence

A chromosomal disorder occurs when there is a change in the number or structure of the chromosomes. This change in the amount or arrangement of, the genetic information in the cells may result in problems in growth, development and/or functioning of the body

1systems . The chromosomal abnormalities may occur either during the production of the egg or sperm or early after the baby's conception: a

2,3spontaneous occurrence for unknown reasons .

Professor,

Department of Oral Pathology & Microbiology,

VSPM Dental College & Research Centre,

Nagpur – 440019. Mob. : + 91 8149336195

E-mail : [email protected]

Shubhangi Khandekar, Alka Dive, Prashant Munde

Introduction

Dr. Shubhangi Khandekar

Chromosomal abnormalities may also be inherited from a parent.

There are two main types of chromosomal disorders: changes in chromosome number and changes in chromosome structure

Chromosomal disorders

Major category of human disease, represent 1% of live births, 2% of pregnancies in women older than 35, 50% of all spontaneous first trimester abortions, responsible for more than 100 human syndromes and are more common than all

5Mendelian single-gene disorders .

Chromosomal abnormalities

sometimes also called cytogenetic disorders – are very common. Most fetuses with some chromosomal abnormality usually do not survive. About 50% of first–trimester abortions

Central India Journal of Dental Sciences, - 201Vol. 4 (1), Jan Mar 335

are connected with some cytogenetic mistake. The incidence of chromosomal abnormalities is

1approximately 1 out of 200 of newborns .

We are able to find the disorders due to karyotype testing. The cytogeneticists get the samples (blood, amnionic fluid), then stain the chromosomes and arrange them in the right order by their length. Then we can see some changes in pattern (banding). The most typical method is giemsa stain, so it is usually called "g banding". This is important for structural abnormalities. Numeral abnormalities we can

6, 7identify even easier .

Other c lass i f icat ion of chromosomal abnormalities depends on fact which type of chromosome is affected – autosomes (down syndrome, digeorge syndrome) or sex chromosomes (klinefelter syndrome, turner syndrome).

Etiology of chromosome abnormalities

Etiology of chromosome abnormalities is pretty variable. The most often reason is mistake which occurs during the cell division. It is connected with wrong development of the sperm or ovum

4(female reproduction cell) .

There are two types of cell division – mitosis and meiosis. Other causes are the maternal age and the influence of the environmental.

Chromosome abnormalities are usually fatal. Each second first-trimester abortion is caused by them. Children who survive and get born suffer from very serious mental and physical

5problems . The screening for chromosome abnormalities is very important. The

6cytogeneticists use the karyotype testing .

Problems in the cell division

There are two main types of the cell division. The first one is the meiosis. It is the process of division of reproduction cells. The result is a cell with 23 chromosomes (it is haploid). Fetus gets

23 chromosomes from the mother and 23 chromosomes from the father. Cells of fetus are already diploid (2n). Mistake during meiosis leads to incorrect number of the chromosomes

5in the egg or in the sperm . Child can get some extra chromosome (trisomy) or miss it (monosomy).

The second type of cell division is the mitosis. It occurs in all non-reproductive cells. It is a form of duplication of the genetic information, followed by the halving of material. The parent cell has 92 chromosomes (4n), two subsidiary cells have 46 Chromosome each (2n).Mitosis starts immediately after fertilization and

6,7continues throughout whole life . When mistake occurs, the chromosomes may not be equal. Problems in mitosis lead to the mosaicism more often.

Age of parents

There is strong influence of the maternal age (especially in Down syndrome). The paternal age is less important, but still has its importance. The difference is in cell division of reproduction

1cells . The number of eggs (female´s cells) is done by our birth. So eggs underway meiosis many times. The later age of delivery means the higher risk of some abnormalities. It takes just 72 hours to the development of sperm cells. It is less

3probably to make a mistake during this period .

Fig. 1 - Problems in the cell division

Parent Cell(2N)

Parent Cell(2N)

Daughter Cell(2N)

DaughterCell (N)

Mitosis Meiosis


To the older women is recommended to visit some genetic counseling centre. "The older women" means more than 35 years. The prenatal diagnosis is the best way to find some affected children. The method of prenatal

5diagnosis as an amniocentesis .

Influence of the environment

It is very hard to tell how important the environmental is. We can´t find any significant differences between parents with child with a chromosome abnormality and parents with healthy child. They have usually very similar lifestyle or habits.5 But there are still some dangerous influences – x-rays, medication or food. Most of them have a cumulative character.

Because we are not sure about the origin of abnormalities, it is hard to recommend any prevention. Sometimes it is said that the folic acid has a positive role in prevention of congenital abnormalities. Pregnant women

7should also get vitamins to reduce risks .

Types of structural abnormalities

TranslocationDuring translocation, a part of one chromosome is transferred to another chromosome. It is very important whether the translocation is balanced or unbalanced. Balanced means that two chromosomes just exchange their parts but the

number of chromosomes (46 chromosomes) as well as no loss of genetic material stays the

2,3same .

Fortunately – typical place of break is near the centromere, usually only small arms of the acrocentric chromosomes are lost. There are no crucially important genes coded by these chromosomal segments. So, a carrier of such robertsonian translocation can normally survive this cytogenetic change.

Unfortunately problems occur during the fertilization with a gamete of a carrier of a balanced translocation. Carrier of the translocation may produce unbalanced zygotes, because the process of homologous chromosomes pairing during meiosis is interrupted. This is very important because unbalanced gametes lead to abnormalities in offspring. The reason is that the offspring receives altered chromosome from the carrier

6which may lack several important genes .

Therefore the only clinical symptom found in the carriers of balanced translocations may be the reproduction failure.

Fig. 2 - Relation between maternal age &development abnormalities

Karyotype44,XY

Balanced trans location

Chromosomal breaks

Karyotype44,XYChromosome

is too small

Robertsonian trans location

Fig. 3 - Translocation


Types of translocation

Reciprocal – translocation between two chromosomes ("a segment" goes to "b chromosome" and "b segment" goes to "a chromosome")

Robertsonian – translocation (or fusion) of two acrocentric chromosomes

Deletion

Deletion is characterized by the loss of a part of chromosome. Two breaks have to occur for deletion of the interstitial segment. For deletion of terminal segment (telomere) one break is enough. Segments which were deleted from the chromosome are not able to "live" on their own and the genes present in those segments are lost.

One special example of deletion exists. It is called "ring chromosome". It is a situation when chromosome lost both of its ends. The long and the small arms then connect together and chromosome became a ring shaped.

Isochromosomes

Isochromosomes are created by the incorrect division of centromere. Normally centromere divides vertically. In this case it divides horizontally.

The result is usually the loss of one arm. It means that newly created chromosome has just two long arms or two short arms which are normally connected by centromere. It occurs relatively frequently in X chromosome. It is a huge problem during the fertilization. Because fetus then becomes trisomic for one arm and monosomic for the second arm.

Inversion

For inversion are typical two breakages in the different part of the chromosome. The newly created segments then replace each other. Inversion was discovered in 1921. Although we still don´t know why inversion exists, we know that it is the most important mechanism of reorganizing of the genome.

There are 2 types of inversion:

Pericentric – causing deletions, insertions or abnormal centromere;

Paracentric – more common type, it is less harmful for its carrier.

Inversion suppresses the recombination process.

Segment

ChromosomeAberration

Chromosomal breaks

Fig. 4 - Robertsonian translocation

Chromosome Ring chromosome

SegmentEnds of chromosome

Fig. 5 - Ring chromosome

Short arm

Centromore

HorizontalDivision

Long arm

Two short arm

Isochromosome

Two long arm

Fig. 6 - Isochromosome


Parts of a chromosome

When we want to describe the location of some structural abnormality we used special marks. We have to count the regions always from the centromere – for both arms. Example: 1q13

The first number is a number of chromosome – chromosome 1;

(p) and (q) are used for marking of arm – (p) for small arm and (q) for long arm – the long arm;

The third number is for the region of chromosome – region 1;

Chromosomal marking last number is for the band – band 3. So the change is located on the long arm of chromosome 1

Abnormalities in chromosomalnumber

Nondisjunction - Mistake in cell division where chromosomes do not separate properly in anaphase.Usually in meiosis, although in mitosis occasionally. In meiosis, can occur in anaphase I or II.

Polyploidy – complete extra sets (3n, etc.) – fatal in humans, most animals.Aneuploidy – missing one copy or have an extra copy of a single chromosome. Three copies of a chromosome in your somatic cells: TRISOMY. One copy of a chromosome in your somatic cells: Monosomy Most trisomies and monosomies are lethal well before birth in humans; exceptions covered below. Generally, autosomal aneuploids tend to be spontaneously aborted. Over 1/5 of human pregnancies are lost spontaneously after implantation.Chromosomal abnormalities are the leading known cause of pregnancy loss. Data indicate that minimum 10-15% of conceptions have a chromosomal abnormality. At least 95% of these conceptions spontaneously abort (often without being noticed)

Aneuploidy in humansex chromosomesX_ female (Turner Syndrome)

Short stature; sterile (immature sex organs); often reduced mental abilities. About 1 in 2500 human female births

XXY male (Klinefelter syndrome)

Often not detected until puberty, when female body characteristics develop. Sterile; sometimes reduced mental abilities; testosterone shots can be used as a partial treatment; About 1 in 500 human male births.

XYY male (XYY syndrome)

Usually tall, with heavy acne; some correlation with mild mental retardation and with aggressiveness; usually still fertile. About 1 in 1000 human male births

XXX female (triple X syndrome)

Usually just like XX females, except for having 2 Barr bodies in somatic cells. HOWEVER, more likely to be sterile, and if fertile, more likely to have XXY and XXX children. About 1 in 1000 human female births. Aneuploidy in human autosomes

Autosomic monosomy

appears to be invariably fatal, usually very early in pregnancy. Most autosomic trisomy is fatal, but sometimes individuals trisomic for autosomes 13, 15, 18, 21, or 22 survive to birth and even beyond. Chromosome number reflects size; bigger number = smaller size, and usually fewer genes. Extra 13, 15, or 18 lead to multiple defects and usually death well before 1 year of age. Extra 22 is much like extra 21 (Down syndrome, covered below), but usually more severe, with shorter life expectancy.


Trisomy 21 (Down syndrome)

The only autosomal trisomy condition in humans that allows an appreciable number of individuals to survive to adulthood Found in about 1 in 750 live births.

A phenotypic ally identical condition occurs that is not due to a true trisomy (it involves a chromosomal translocation, covered later)

Traits include abnormal facial appearance, high likelihood of mental retardation (degree varies considerably), and increased likelihood of developing leukemia and Alzheimer's disease

Likelihood of a child being born with Down syndrome increases with the age of the mother rate is as high as 1 in 16 live births for mothers age 45 and over at conception. Not completely clear why the odds go up so dramatically, likely a combination of factors. It is clear that Nondisjunction is more common in eggs than sperm.Appears that spontaneous rejection of aneuploids pregnancies is more common in younger women.

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Source of Support : Nil, Conflict of Interest : None declared
