Chromosome

I. NORMAL CHROMOSOME

Chromosomes are the factors which distinguish one species from another. Enable transmission of genetic information from one generation to the next.

General Structure of Choromosome :Chromosome consist of two identical strands known as chromatids or sister

chromatids. The sister chromatids joined at a constriction known as centromere. Centromere consist of repetitive DNA, are responsible for movement of chromosomes. Centromere divides chromosomes into short arms (p=petite) and into long arms (q=grande). The tip of each chromosome arms is telomere.

A single Chromosomes consists of 2 characteristic regions called arms,which are separated by a centromere. During Meiosis I , a single chromosomes undergo DNA replication, which essentially duplicateds tha arms forms duplicated chromosomes, which consist of 2 sister chromatids attached at the centromere. The chromosomes in somatic cells are normally paired : they are called homologous chromosomes (homologs)

Normal somatic cell:

- contain 46 single chromosomes and 2N amount of DNA; - the chromosome occur in 23 homologus pairs, 1 member of each pair is of maternal

origin and the other is of paternal origin. - pairs 1-22-----autosomal pairs (non sex) - pair 23 consists of the sex chromosomes(XX for a female or XY for a male) - diploid refers to a cell containing 46 single chromosomes. - Gametes: Contain 23 single chromosomes (22 autosomes and 1 sex chromosome) and

1N amount of DNA. haploid refer to a celll containing 23 single chromosomes.

Normal human females have 22 pairs of autosome plus two X chromosomes, whereas normal males have 22 pairs of autosomes plus one X chromosome and one Y chromosome.

According to the position of the centromere, chromosomes are classified a metacentric, submetacentric, acrocentric, telocentric. Metacentric : the centromere is located centraly. Submetacentric : the centromere is located between the central and the terminal. Acrocentric : centromere is located in the terminal. Sometimes acrosentric have

appendages called satellite. Satellite consists of very large series of simple short tandemly repeated DNA sequences which are transcriptionally inactive. Satellite are clustered around the centromere of certain chromosomes.

Telocentric : The centromere is present at one end hence one arm is almost equal to the length of the chromosome while the other is iike a dot.

The Sex Chromosome.The X and Y chromosomes are known as the sex chromosome because of their role

in sex determination. In humans both the male and female have two sex chromosomes: XX in female and XY in male. The Y chromosome is much smaller then X. Each ovum carries an X chromosome, whereas sperm carries either an X or a Y chromosome. An equal chance in X bearing sperm or Y bearing sperm in fertilizing an ovum. The number of male and female conception are approximately equal.

Classification of ChromosomeIndividual chromosomes differ not only in the position of the centromere but also in

their overall length. In human the normal cell nucleus contains 46 chromosomes, made up of 22 pairs of autosomes and single pair of sex chromosomes – xx in the female and xy in the male. Individual chromosome subdivided into groups labelled from A to G. The sex chromosomes X and Y in the last number. Group A (1 – 3): Large chromosomes with approximately median centromeres. Group B ( 4 – 5) : Large chromosomes with sub median centromeres. Group C ( 6 – 12 ) : Medium sized chromosomes with sub median centromeres. X

chromosome is similar to C chromosomes.

Group D (13 – 15) : Medium sized chromosomes with nearly terminal centromeres ( acrocentric ). Chromosome number 13 has prominent sattelite on the short arms, number 14 has small sattelite on the short arms and number 15 has no sattelite.

Group E (16 – 18) : Rather short with approximately median or sub median centromeres.

Group F (19 – 20) : Short chromosomes with approximately median centromere. Group G (21 – 22): Very short, acrocentric chromosomes. Y chromosome is similar to

this chromosomes.

II. CHROMOSOMES ABNORMALITIESTwo kinds of change occur in chromosome complements : numerical and structural. The

changes may affect the sex chromosomes and/or the autosomes. Numerical abnormality involve the loss of one or more chromosomes referred to as

aneuploidy. The addition of one or more chromosomes referred as polyploidi. Lost of a single chromosome is known as monosomy; gain of one homolog chromosome is known as trysomy and gain of two chromosomes is tetrasomy. The changes in chromosomes were associated with phenotypic (morphologic characteristics) anomalies, inviability of zygotes or death of early embryo.

Numerical aberrations of chromosomes usually result from non-disjunction, an error in cell division in which there is failure of a chromosomal pair or two chromatids of a chromosome to disjoin during mitosis or meiosis.

Non Disjunction

o Aneuploidy and PolyploidyChanges in chromosome number represent either aneuploidy or polyploidy.

Aneuploidy is any deviation from the human diploid number of 46 chromosomes. An aneuploid is an individual who has a chromosome number that is not an exact multiple of the haploid number of 23. A polyploid is an individual who has a chromosome number that is a multiple of the haploid number of 23 other than the diploid number The principal cause of aneuploidy is nondisjunction during cell division resulting in an unequal distribution of one pair of homologous chromosomes to the daughter cells. One cell has two chromosomes and the other has neither chromosome of the pair. As a result, the embryo's cells may be hypodiploid (45, X, as in Turner syndrome) or hyperdiploid (usually 47, as in trisomy 21 or Down syndrome). Embryos with monosomy-missing a chromosome-usually die. Approximately 99% of embryos lacking a sex chromosome (45, X) abort spontaneously.

o Trisomy • The presence of three chromosome copies in a given chromosome pair is called

trisomy. Most cases of Down’s syndrome are due to the present of an additional number 21 chromosomes, often known as trisomy21.

• The usual cause of this numerical error is meiotic non-disjuntion of chromosomes, resulting in a gamete with 24 instead or 23 chromosomes and subsequently in a zygote with 47 chromosomes.

• Other autosomal trisomy is Patau’s syndrome (trisomy13) and Edward’s syndrome (trisomy18). Most other autosomal trisomies results in first threemester spontaneous miscariages (trisomy16).

o Tetrasomy and PentasomyPersons with these abnormalities have four or five sex chromosomes, respectively;

the following chromosome complexes have been reported in females: 48, XXXX and 49, XXXXX; and males: 48, XXXY, 48, XXYY, 49, XXXYY, and 49, XXXXY. The extra sex chromosomes do not accentuate sexual characteristics; however, usually the greater the number of sex chromosomes present, the greater the severity of mental retardation and physical impairment.

Stuctural Abnormalities. Structural chromosome rearrangements result from chromosome breakage with subsequent reunion in different configuration. In balance rearrangements the chromosome complement is complete with no loss or gain of genetic material. In unbalance rearrangements the chromosomal complement contains an incorrect amount of chromosome material.

- Translocations Translocations refers to the transfer of genetic material from one chromosome to

another. Reciprocal translocation is formed when a break occurs in each of two chromosomes with the segments being exchanged to form two new derivative chromosomes. Robertsonian translocation is a particular type of reciprocal translocation which the break-points are located at or close the centromeres of two acrocentric chromosomes. A ring chromosome is a type of deletion chromosome from which both ends have been lost, and the broken ends have rejoined to form a ring-shaped chromosome.

- DeletionA deletion involves loss of part of a chromosome and results in monosomy for the

segment of the chromosome. The syndrome caused by the deletion chromosomes described as the Wolf-Hirschhorn and Cri du chat syndromes which caused by losing of material from the short arms of chromosomes 4 and 5 respectively. In both conditions there are severe mental retardation.

- InsertionsAn insertion occurs when a segment of one chromosome inserted into another

chromosome. An insertion can causes an unbalanced chromosome complement. Carriers of a balanced deletion-insertion rearrangement are at a 50% risk of producing unbalanced gametes. Inheriting either deletion or insertion but not both.

- InversionAn inversion is a two-break rearangement involving a single chromosome in which a

segment is reversed in position, i.e. inverted. A pericentric inversion occurs if the inversion segment involves the centromere. A paracentric inversion occurs if it involves only one arm of the chromosome. Inversion is rarely cause problems in carries, unless one of the break-points has disrupted an important gene. Polymorphism or heteromorphism is a common structural variant,occurs when a pericentric inversion involving chromosome number 9.

- DuplicationIs a presence of a chromosomal segment more than once in the same chromosome.

There is additional of chromosome part. The way of duplication can occur when a broken segment from one chromosome attached to its homologous. It can be an unequal crossing-over, leading to duplication and deletion. Chromosome duplications are usually lethal.

- IsochromosomesThe abnormality resulting in isochromosomes occurs when the centromere divides

transversely instead of longitudinally. An isochromosome is a chromosome in which one arm is missing and the other duplicated. An isochromosome appears to be the most common structural abnormality of the X chromosome. Persons with this abnormality are often short in stature and have other stigmata of Turner syndrome. These characteristics are related to the loss of an arm of an X chromosome.

Annisa Dwi Khairina 130110110143

References :

- Muller, R.F and Young, I.D : Emery’s Element of Medical Genetics. 2001.

A.Reciprocal translocation B.Terminal deletion C.Ring Chromosome D.Duplication E.Paracentric Inversion F.Isochromosome G.Robertsonian

translocation

- Keith L moore,T.V.N. Persaud. The Developing Human Clinically Oriented Embryology 6th Ed. WB Sounders company. 1998. p. 329 -330