Chromosome Aberrations

CHROMOSOMAL ABERRATIONS: 

CHROMOSOMAL ABERRATIONS Dr. Balina Moses balina55@live.com 0754477446

CHROMOSOMAL ABERRATION: 

CHROMOSOMAL ABERRATION Is an abnormality of chromosome number or structure.

Chromosomal Aberration: 

Chromosomal Aberration Classification of Chromosomal Aberrations May be either numerical or structural May affect either autosomes or sex chromosomes

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 1.Numerical Aberrations Arise chiefly through the process of nondisjuntion (failure of paired chromosomes or sister chromatids to disjoin at anaphase, either in a mitotic division or in the 1 st or 2 nd meiotic divisions). Anaphase lag, when the members of a chromosome pair fail to synapse & therefore do not move apart correctly on the spindle, is a type of non disjunction that can result in one member of a pair failing to be included in either daughter cell. Any species has a characteristic chromosome number (in man, 2 n =46 & n =23) Any number that is an exact multiple of the haploid is euploid. Chromosome numbers such as 3 n (triploid) & 4 n (tetraploid), which are exact multiples of n but greater than 2 n , are said to be polyploid.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 1.Numerical Aberrations Triploidy results from failure of one of the maturation divisions, either in ovum or sperm. Tetraploidy results from failure of completion of the 1 st cleavage division of the zygote. Any number that is not an exact multiple of n is aneuploid. Some types of aneuploids are trisomics, with 2 n +1 chromosomes & 3 members of one particular chromosome, as in Down syndrome; monosomics, with 2 n -1 chromosomes & only one member of some chromosome; double trisomics (2 n +1+1), with an extra member for each of two chromosomes & so forth. Any chromosome number that deviates from the characteristic n & 2 n is heteroploid, whether it is euploid or aneuploid.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 1.Numerical Aberrations Aneuploidy The chief cause of aneuploidy is nondisjunction in a meiotic division, leading to unequal distribution of one pair of homologous chromosomes to the daughter cells so that one daughter cell has both & the other has neither chromosome a pair. Failure of pairing of two homologous chromosomes, followed by their random assortment rather than segregation, can have the same result. Nondisjunction can also occur at mitosis after formation of the zygote, in which case the nondisjoining objects are the chromatids of a single chromosome, as in meiosis II.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Structural rearrangements result from chromosome breakage, followed by reconstitution in an abnormal combination. Chromosome breakage may be induced by breaking agent (clastogens) such as ionizing radiation, some virus infections & many chemicals. The changes in chromosome structure resulting from breakage may be either stable (i.e.,capable of passing through cell division unaltered) or unstable. The stable types of aberration are deletions, duplications, inversions, translocations, insertions & isochromosomes. The unstable types, which fail to undergo regular cell division, are dicentrics, acentrics & rings.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Deletion Deletion is loss of a portion of a chromosome, either terminally following a single chromosome break, or perhaps more often interstitially between two breaks. The deletion portion, if it lacks a centromere, is an acentric fragment, which because it has no centromere fails to move on the spindle, & is eventually lost at a subsequent cell division. E.g., of deletion in humans is the cri du chat syndrome, in which part of the short arm of chromosome 5 is deleted. A ring chromosome is a type of deletion chromosome in which both ends have been lost & the broken ends have reunited to form a ring. If it has a centromere, a ring chromosome can pass through cell division, but it may undergo alteration in structure.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Duplication Duplication is the presence of an extra piece of chromosome, which usually has originated by unequal crossing over. Duplication of parts of chromosomes may occur as a consequence of various structural rearrangements. E.g., if a patient is a translocation heterozygote, unbalanced gametes may be formed which have, in effect, a duplication of one segment & deletion of another. Partial duplications also result from crossing over in inversion heterozygotes, or from isochromosome formation.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Inversion Inversion involves fragmentation of a chromosome by two breaks, followed by reconstitution with inversion of the section of the chromosome between the the breaks (ABCDEFGH might become ABCFEDGH). If the inversion is in a single chromosome arm it is paracentric (beside the centromere), but if it involves the centromere region it is pericentric (around the centromere).

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Translocation Translocation is the transfer of part of one chromosome to a nonhomologous chromosome. The process requires breakage of both chromosomes, with repair in an abnormal arrangement. A balanced translocation does not necessarily lead to an abnormal phenotype, nut, like, inversions, translocations can lead to the formation of unbalanced gametes & therefore high risk of abnormal offspring. Robertsonian translocations are a special type in which the breaks occur at centromeres & whole chromosome arms are changed. An insertion is a type of translocation in which a broken part of a chromosome is inserted into a nonhomologous chromosome.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 2.Aberrations of Chromosome Structure Isochromosomes During cell division, the centromere of a chromosome sometimes mistakenly divides so that it seperates the two arms rather than the two chromatids. The chromosomes so formed are isochromosomes. The most common kind of isochromsome is for the long arm of X & is designated Xqi.

Classification of Chromosomal Aberrations: 

Classification of Chromosomal Aberrations 3. Mosaics If nondisjunction happens at an early cleavage division of the zygote rather than during gametogenesis, an individual with two or more cell lines with different chromosome numbers is produced. Such individuals are termed mosaics. A chromosome mosaic has at least two cell lines, with different karyotypes, derived from a single zygote. The alterations in the karyotype may be either numerical or structural.

Causes of Chromosomal Aberrations: 

Causes of Chromosomal Aberrations Late maternal age Genes predisposing to nondisjunction Autoimmune disease Radiation Is a major factor in the etiology of Down syndrome &, to a lesser extent, of the other trisomies. Probably exist in man, since such genes are known in other organisms. Seems to have some role in pathogenesis of nondisjunction, in view of an observed correlation between high thyroid autoantibody levels & chromosomal anomalies in families Has been postulated as a cause of nondisjunction..

Causes of Chromosomal Aberrations: 

Causes of Chromosomal Aberrations 5. Viruses 6. Chromosome abnormalities Have also been shown to cause breakage of chromosomes. Themselves lead to abnormal segregation of chromosomes.

Clinical Aspects of Autosomal Disorders: 

Clinical Aspects of Autosomal Disorders [1]. Cri du Chat Syndrome (5p-) Deletion of part of the short arm of chromosome 5 results in this syndrome named because of the resemblance of the cry of an affected child to the mewing of a cat. The facial appearance is distinctive, with microcephaly, hypertelorism, antimongoloid slant of the palpebral fissures, epicanthus, low-set ears sometimes with preauricular tags, & micrognathia. The dermal patterns of the palms, fingers & soles are also characteristic, with simian creases, a high total ridge count & a high frequency of thenar patterns. Severe mental retardation, failure to thrive, hypotonia & low birth weight despite normal gestation time. Most cases are sporadic, but 10 to 15% are the offspring of translocation carriers. Mosaicism, with a normal cell line & 5p- line, has been observed.

Clinical Aspects of Autosomal Disorders: 

Clinical Aspects of Autosomal Disorders [2]. Trisomy 13 (D Trisomy) The phenotype includes severe CNS malformations such as arhinencephaly & holoprosencephaly. Growth retardation & severe mental retardation are present. The forehead is sloping, there is ocular hypertelorism, & there may be microphthalmia, iris coloboma or even absence of the eyes. The ears are malformed. Cleft lip & cleft palate are often present. The hands & feet may show postaxial polydactyly & an unusual clenching pattern, with the 2 nd & 5 th fingers overlapping the 3 rd & 4 th . The feet are “rock-bottom,” with prominent calcanei. Internally, there are usually congenital heart defects & urogenital defects.

Clinical Aspects of Autosomal Disorders: 

Clinical Aspects of Autosomal Disorders [3]. Trisomy 18 (E Trisomy) Features include mental retardation & failure to thrive. Hypertonia. The head has a prominent occiput, & the jaw recedes. The ears are low-set & malformed. The sternum is short. Congenital malformations of the heart.

Clinical Aspects of Autosomal Disorders: 

Clinical Aspects of Autosomal Disorders [4]. Trisomy 21 (Down Syndrome) Children with Down syndrome have 47 chromosomes, the extra member being a small acrocentric that has since been designated chromosome 21. The older name of mongolism, now falling into disuse, refers to the somewhat Oriental cast of countenance produced by the characteristic epicanthal folds, which give the eyes a slanting appearance. Phenotypic features include Hypotonia. Mental retardation is present, the I.Q. Is between 25 to 50 range. The head is brachycephalic, with a flat occiput. The eyes have epicanthal folds, & the iris shows speckles (Brushfield spots) around the margin. The nose has a low bridge. The tongue usually protrudes & is furrowed, lacking a central fissure.

Clinical Aspects of Autosomal Disorders: 

Clinical Aspects of Autosomal Disorders [4]. Trisomy 21 (Down Syndrome) -Continued. The hands are short & broad, usually with a simian crease & clinodactyly (incurving) of the 5 th finger. On the feet, there is often a wide gap between the 1 st & 2 nd toe & a furrow extending proximally along the plantar surface. About one-third of the patients have congenital malformations of the heart.