CHROMOSOMAL ABERRATION.a detailed presentation

Chromosomal aberration

1. CHROMOSOMAL ABERRATION AISWARYA RAJAN 1 MSC ZOOLOGY UNIVERSITY OF CALICUT

2. INTRODUCTION Chromosomal mutations are abnormal structural and numerical changes of chromosomes, thus called as chromosomal aberrations. There are two types of chromosomal aberrations, they are; Structural Aberrations – Gross structural changes of chromosomes Numerical aberrations – Ploidy or numerical changes of chromosomes

3. STRUCTURAL ABERRATION Structural changes of chromosomes involves the gain, loss, or relocation of chromosome segments and genes. In effect, they bring about changes in the number and arrangement of genetic loci, with marked genetic effects. Structural aberrations are of four basic types, namely, DELETION DUPLICATION INVERSION TRANSLOCATION

4. DELETION Deletion is the loss of a chromosome segment, together with the genes contained in it. It is also known as deficiency. Loss of terminal segment with a single break in the chromosome is called terminal deletion . Loss of an intercalary segment with two break in the chromosome is called intercalary deletion. In any case the lost segment would be acentric, that is, without centromere. Deletion often results in abnormal phenotype or lethality.

5. A B C D E F G Break A B C D E F G Deficiency with single break is known as terminal deletion which involves loss of terminal segment. TERMINAL DELETION INTERCALARY DELETION Break B C A D E F G Deficiency with double break is known as intercalary deletion which involves loss of intercalary segment.

6. TYPES OF DELETION Homozygous deletion- A segment is lost from both the chromosomes of a homologous pair. It is most usually lethal. Heterozygous deletion- A segment is lost from one of the two homologues. It mainly causes abnormal phenotype. Meiotic pairing of homologous with heterozygous deletion involves the formation of an unpaired loop or bulge in the normal chromosome. The loop is formed in the region which corresponds to the lost part of the deficient chromosome.

7. GENETIC EFFECTS OF DELETION Deletions involve loss of genes. The intensity of their effects depends on number and quantity of lost genes. Heterozygosity for small deletions are usually viable, but abnormal. However, homozygosity for small deletions may have lethal effects. Pseudodominance – Some heterozygous deletions involve the loss of dominant alleles, without effecting their counterparts in other homologue. This often results in the expression of persisting recessive alleles. The expression of recessive alleles due to deletion of the dominant allele is called pseudodominance. Example – Waltzing mouse – It is the mouse which moves about erratically until it gets exhausted, is a result of pseudodominance.

8. In human genome, deletion mutation results in drastic phenotypic changes. Granulocyte leukemia- It is caused due to the deletion in the long arm of chromosome 21. This is non-heritable somatic mutation, occurs when there are too many granulocytes in the blood. It’s a condition that’s closely related to chronic myelogenous leukemia (CML) and other bone marrow disorders. Granulocytes are white blood cells that have small granules or particles. Cri-du-chat syndrome- It is a well known case of deletion mutation in man. Also called Cat- cry syndrome. Caused by the heterozygous deletion in the short arm of Chromosome 5. The effected children are mentally retarded and they cry just like a cat mews. The disorder is characterized by intellectual disability and delayed development, small head size ,low birth weight, and weak muscle tone (hypotonia) in infancy. A lso have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect.

9. DUPLICATION Duplication is the doubling or repetition of a chromosome segment during chromosome duplication. So, in this case a set of gene exist more than once, and this extra set is generally called repeat. The duplicate segment may be incorporated either with the parent chromosome or with another chromosome or it may exist as a separate piece. Duplications are believed to be an important raw material for organic evolution.

10. TYPES OF DUPLICATION Tandem duplication - The extra segment and the parent segment are next to each other and both of them have the same polarity or order of genes. Reverse tandem duplication -The extra segment lies next to the parent segment with reversed polarity or reverse gene sequence. Displaced duplication - The duplicate segment lies some distance away from the parent segment or it gets translocated to a non-homologous chromosome. Duplication can be two kinds, namely, Homozygous duplication - both the homologous of a a pair of chromosome will have homologous duplicate sequence. Heterozygous duplication -only one of the pairs of chromosomes will have a duplicate sequence.

11. A B B B A A C D E F A B B A C D E F A B C D A B E F H I J K A B L TANDEM DUPLICATION REVERSE TANDEM DUPLICATION DISPLACED DUPLICATION IN SAME CHROMOSOME DISPLACED DUPLICATION IN DIFFERENT CHROMOSOME DUPLICATE SEGMENT EXIST AS A NEW CHROMOSOME

12. GENETIC EFFECTS OF DUPLICATION A classical example of tandem duplication is the ‘ bar eye’ of drosophila. The normal eye of female drosophila is oval, whereas, its bar eye is like an oblong narrow bar. Bar eye is shown due to duplication at a specific site in the X chromosome called , Bar Locus 16A . This locus contains the dominant allele for normal eye. The narrowness of the eye is directly proportional to the number of duplications of the bar locus. In duplication heterozygous- the eye becomes smaller and narrower than normal eye; that is the bar eye. In duplication homozygous- the eye become extremely small and narrow; that is the double bar eye. Any further duplication of bar locus would make the eye still narrower.

13. INVERSION Inversion is the reversal of the linear orientation of a chromosome segment and the order of its gene sequence. Inversion is exclusively found in the intercalary segments. It involves breakage of a chromosomal segment and its subsequent re-insertion into the same location in a reversed orientation. Normally, two breaks occur in the chromosome and are called inversion points.

14. TYPES OF BREAKS Paracentric breaks- The break exclude the centromere, and both the breaks occur on one side of the centromere in the same arm. The break separates an acentric arm. Rotation and re-insertion of an acentric segment is called paracentric inversion. Pericentric breaks- The break include the centromere, and they occur one on either side of the centromere, so one in each arm. The break separates a centric arm. Rotation and re-insertion of a centric segment is called pericentric inversion.

15. E F E F A B C D E F A C B D A B C D A B E D C F Break Rotation at 180 PARACENTRIC INVERSION Break Rotation at 180 PERICENTRIC INVERSION

16. GENETIC EFFECTS OF INVERSION The effects of inversion are not so drastic as those of deletion and duplication. One of the best-characterized recurrent inversions giving rise to disease causes hemophilia A, an X-linked disorder caused by mutations in the factor VIII gene. A recurrent inversion has been found in approximately 43% of patients. Produces phenotypic changes due to change in location of genes. Inversion serves as a crossing over suppressor and reduces crossing over frequency.

17. TRANSLOCATION Translocation is the chromosomal aberration which involves the re-organization of chromosomes through the transfer or change in position of chromosome segment without gain or loss of genes. It involves transfer of a segment from one location to another in the same chromosome or from one chromosome to a non-homologous one.

18. TYPES OF TRANSLOCATION Intrachromosomal translocation- It is a three break aberration resulting in change of position of a segment within a chromosome, either from one arm to other or from one location to another in same arm. It is also know as internal translocation or chromosomal shift. Interchromosomal translocation- It is the transfer of a segment from one chromosome to another. It is of two types; Transpositional / Interstitial translocation– Non-reciprocal one way transfer of chromosome segment from one chromosome to another. Reciprocal / Mutual / Inter-change translocation– Mutual exchange of segments between two chromosomes, either homologous or non-homologous.

19. A B C D E F A D E B C F Break INTRACHROMOSOMAL TRANSLOCATION INTERCHROMOSOMAL TRANSLOCATION A B C D E F M N O P A D E F M B C N O P A B C D E F M N O P Q R A N O D E F M B C P Q R TRANSPOSITIONAL TRANSLOCATION RECIPROCAL TRANSLOCATION

20. GENETIC EFFECTS OF TRANSLOCATION Causes change in chromosomes and gene combinations, alters linkage relationship of genes etc. Translocation mainly leads to infertility, miscarriages, or children with abnormalities. Several forms of cancer are caused due to the translocation of chromosome segments, mainly leukemia.

21. NUMERICAL ABERRATION Numerical aberration is also known as ploidy changes. They involve gain or loss of either individual chromosomes or monoploid set of chromosome. The major cause of ploidy changes is non- disjunction. Numerical aberration are two basic types; EUPLOIDY ANEUPLOIDY

22. EUPLOIDY Euploidy changes involves the duplication or loss of one or more monoploid sets. Euploidy includes Monoploidy – The somatic cells contain only one basic set of chromosomes. Diploidy – The somatic cells contain two basic set of chromosomes. Polyploidy – The somatic cell contains more than two basic genome set. It is of two types; Autopolyploidy- Condition in which the multiple genomes are identical and derived from the same species. Allopolyploidy- Condition in which the multiple genomes are distinctly different and derived from different species through hybridization.

23. SIGNIFICANCE OF POLYPLOIDY Polyploidy serves as a mechanism of speciation and evolution. Autopolyploidy is found in many plants, allopolyploids are mainly hybrids such as mule. They are significant in agriculture and horticulture.

24. ANEUPLOIDY Aneuploidy is the condition in which individual chromosomes or chromosome pairs are added to or lost from the somatic chromosome compliment. It usually results from mitotic or meiotic non-disjunction. Aneuploidy is of two kinds; HYPOPLOIDY – It is the aneuploidy due to chromosome loss. Monosomy- One chromosome is lost from diploid set, (2n-1). Example – Turner’s syndrome (XO) Nullisomy – Loss of a homologous pair of chromosome from a somatic set, (2n-2). They often don’t survive.

25. 2. HYPERPLOIDY – It is the aneuploidy due to chromosome gain. Also known as polysomy. Trisomy – Addition of an extra chromosome to a diploid set. (2n+1) Example: Down’s syndrome – Trisomy 21 Edward’s syndrome – Trisomy 18 Patau’s syndrome – Trisomy 13 Klinefelter’s syndrome – (XXY) Tetrasomy – Addition of a homologous pair of chromosome to diploid set. (2n+2) Example: Pallister-Killian syndrome – Tetrasomy 12p Cat-Eye syndrome – Tetrasomy 22

26. REFERENCES Cell and molecular biology – Karp Molecular Cell Biology – Lodish Cell Biology, Classical Genetics, Human Genetics, Molecular Biology- K.K Bhaskaran NORD – National Organization for Rare Disorders www.ncbi.nlm.nih.gov www.sciencedirect.com Genomemedicine.biomedcentral.com