Structural Chromosomal Aberrations PDF

# Structural Chromosomal Aberrations ## Faculty of Veterinary Medicine ### Department of Animal Wealth Development ### Genetics and Genetic Engineering – 1th Level Students Dr/Huda EL Emam ## Structural Chromosomal Aberrations - changes in normal structure of chromosomes or the arrangement of gen...

# Structural Chromosomal Aberrations ## Faculty of Veterinary Medicine ### Department of Animal Wealth Development ### Genetics and Genetic Engineering – 1th Level Students Dr/Huda EL Emam ## Structural Chromosomal Aberrations - changes in normal structure of chromosomes or the arrangement of genetic material within or between individual chromosomes. - Chromosomal structural aberrations result from chromosome breakage and reunion in an abnormal way - Chromosome breakage is caused by X-rays, various chemicals, and can also occur spontaneously. ## Types of Structural Chromosomal abnormalities: | Balanced structural aberrations | Unbalanced structural aberrations | |---|---| | No change in genetic material and usually give normal phenotype | Increased or decreased genetic material and give abnormal phenotype | | Translocations – Inversions | Deletions – Duplications – Insertions | | | Rings – Isochromosomes | ## Unbalanced Structural Aberrations ### 1- Deletions - **Definition**: Part of a chromosome is missed or deleted and occur during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome. - **Deletions do not revert, because the DNA is gone (degraded)**. ### Causes - **Unequal crossing over:** It is a type of chromosomal crossover between homologous sequences that are not paired precisely. - A diagram shows homologous chromosomes crossing over in an uneven fashion, resulting in one chromosome missing a segment and the other chromosome having a duplicated segment. - A diagram shows a pair of homologous chromosomes with a visual representation of misalignment during meiosis and subsequent unequal crossing over. ### 2- Breaking caused due to heat or radiation, Viruses, Chemicals without rejoining. ### 3- Loss from translocation ## Types of Deletion - **Terminal deletion**: a deletion that occurs towards the end of a chromosome. - **Interstitial deletion (Intercalary)**: a deletion that occurs from the interior of a chromosome - **Microdeletion**: are too small to be detected by karyotype. Micro-deletion is usually found in children with physical abnormalities. - A diagram depicts a normal chromosome, followed by a break, resulting in a terminal deletion, and an interstitial deletion. ### Effect of a Deletion: - **Depend on the location and size of deleted part.** - **No known living human has an entire autosome deleted from the genome.** - **Deletion of the centromere results in an acentric chromosome that is lost.** - **Large deletions are usually fatal.** - **Some medium-sized deletions lead to recognizable human disorders, e.g. Williams syndrome, infertility, muscular dystrophy, and cystic fibrosis.** - **Microdeletions are associated with many different conditions, including Angelman Syndrome, Prader-Willi Syndrome, and DiGeorge Syndrome.** - **Deletion of part of the short arm of chromosome 5 results in Cri du chat syndrome.** ## Cri-du-chat (“cry of the cat”) syndrome (CdCS), (5p-syndrome): Resulting from deletion of part of the short arm of chromosome 5 - A diagram depicts a pair of chromosome 5s, with one chromosome showing a shortened short arm, labeled “deleted region”. - **The deletion results in severe mental retardation and physical abnormalities, cry sounds like a cat, low birth weight, slow growth, small head, wide-set eyes, small jaw and low-set ears.** - A side-by-side comparison of a young girl with Cri du Chat syndrome at ages six and sixteen. - A picture of a boy with Cri du Chat syndrome is featured next to a karyotype showing the shortened short arm of chromosome 5 alongside the other chromosomes. - A diagram illustrates a karyotype showing the shortened short arm of chromosome 5 (5p-), labeled as (46,5p-) karyotyping. ## 2- Duplications: - **Definition**: Duplications result from doubling of chromosomal segments or the entire chromosome. - **Causes**: Unequal crossing-over (recombination) - A diagram shows chromosomes with a duplicated area and a karyotype showing a trisomy of chromosome 21. ### Types: 1. **Tandem duplications** are adjacent to each other (ABC,ABC). 2. **Reverse tandem duplications** result in genes arranged in the opposite order of the original (ABC, CBA). 3. **Terminal duplications** at the end of a chromosome (tandem or reverse tandem). - A diagram shows a normal chromosome and 3 variations with tandem, reverse tandem, and terminal duplications. ### 3- Ring chromosome: - **Definition**: Chromosome undergoes 2 breaks and broken ends reunite in a ring. - A diagram depicts a chromosome undergoing 2 breaks, then fusing to form a ring chromosome. - **Causes** Mutagens like radiation, but they may also arise spontaneously during development. ### Examples of human disorders associated with ring chromosome ### Ring chromosome 14 syndrome is a very rare human. - **Symptoms**: - Facial abnormalities. - Immune deficiencies. - Abnormalities of retina. - Slow growth. - A picture of a boy with ring chromosome 14 syndrome. - A diagram depicts a karyotype showing a ring chromosome 14, labeled as (46,14r) karyotyping. ## 4- Isochromosome: - **The chromosome consists of two copies of the same arm (Mirror image around centromere)**. - **It is due to transverse centromere division instead of normal longitudinal division.** - **The isochromosomes seen mostly involving X chromosome.** - A diagram shows a normal separation of chromatids during anaphase, compared to an abnormal division resulting in an isochromosome. ## 5- Insertions - **A portion of one chromosome has been deleted from its normal place and inserted into another chromosome** - A diagram shows a portion of chromosome 20 being inserted into chromosome 4. ## Balanced Structural Aberrations ### 1- Inversions - **Definition**: Inversion results when a chromosome segment excises and reintegrates oriented 180 degrees from the original orientation. - **Types**: Paracentric and pericentric ### 1- Paracentric inversion: - Not include centromere and not change length of arms of chromosome. ### 2- Pericentric inversion: - Include centromere and change length of arms of chromosome. - A diagram depicts a pericentric inversion (including the centromere) next to a paracentric inversion (not including the centromere.). - A diagram compares the structures of paracentric and pericentric inversions, noting that paracentric inversions do not change arm ratio, while pericentric inversions do. ### Effect of inversion: 1. **In inversions there are no extra or missing DNA (the total amount of genetic information stays the same) (balanced).** 2. **Position effect of inversion:** the position of the gene is altered due to its relocation and change in phenotype may occur. **Example:** In drosophila: W red eye w white eye WW (red), Ww (red), ww (white), if inversion occur to W and relocated in an inactive area this lead to Ww become white. ## 2-Translocations - **Definition**: It means that sections of two chromosomes have switched places. - **Types**: - Reciprocal translocation. - Nonreciprocal translocation. - Robertsonian (unbalanced) Translocations. ### 1-Reciprocal translocation - **Refers to the exchange of chromosome segments between non homologous chromosomes.** - **In reciprocal translocation, broken segments of chromosomes exchange between two chromosomes that do not belong to the homologous pair.** - A diagram shows the process of balanced translocation. - A diagram shows a depiction of reciprocal translocation, before and after, with the statement "no gain or loss of genetic information". - **For example, a specific reciprocal translocation takes place between chromosomes 1 and 19, which are not homologous to each other.** - **However, two translocated chromosomes originate at the end of the reciprocal translocation.** - **Furthermore, the places of centromere and the sizes of chromosomes may vary greatly due to reciprocal translocation.** - **Example**: When part of Chromosome 8 breaks off and fuse with part of Chromosome 11, so you have what we call an 8/11 translocated product (one gene on Chromosome 8 will be fused to a different gene of Chromosome 11) so you have a fusion gene. Gene fusion may be created when the translocation joins two otherwise-separated genes. ## 2-Nonreciprocal translocation: - **Nonreciprocal translocation involves the one-way transfer of genes from one chromosome to another non homologous chromosome.** - A diagram shows a portion of chromosome 20 being transferred to chromosome 4, showing a non-reciprocal translocation. - A comparison between reciprocal and non-reciprocal translocations. ## 3. Robertsonian (unbalanced) Translocations (RT): - **A specific class of translocations in which two acrocentric chromosomes fuse at their centric ends. Caused by breaks at or near the centromeres of two acrocentric chromosomes.** - **The RT exchange of parts gives rise to one large metacentric or submetacentric chromosome and one extremely small chromosome that may be lost from the organism.** - A diagram shows the two short arms of acrocentric chromosomes being lost as the two long arms fuse. - A diagram shows the process of robertsonian translocation. - **RT is confined to chromosomes 13, 14, 15, 21.** - A karyotype shows all chromosomes, with chromosome 21 fused with chromosome 14, labeled as 21-14. - A diagram shows a normal chromosome and 5 variations, including a translocation carrier, monosomy 14, trisomy 14, monosomy 21, and translocation Down's syndrome. - **Example**: **Familial (inherited) Down Syndrome** - **In this condition, the majority of chromosome 21 is attached to chromosome 14 (Breaks occurs at the extreme ends of the short arms of two non-homologous acrocentric chromosomes).** - **The baby has three copies of the long arm of chromosome 21 instead of two. This causes a type of Down's syndrome called translocation Down's syndrome. The effects on the baby are exactly the same as when Down's syndrome is caused by having an extra entire chromosome 21.** ## Down Syndrome - **Characterized by the presence of an extra copy of genetic material on chromosome 21, either in whole (trisomy 21) or part (such as due to translocations).** - **Causes**: 1. **95% of down syndrome causes due to trisomy of chromosome 21 due to meiotic non disjunction (random error during cell division) (numerical chromosomal aberration).** - A diagram showing a normal chromosome and 5 variations, including a translocation carrier, monosomy 14, trisomy 14, monosomy 21, and translocation Down's syndrome. 2. **Translocation**: 5% of down syndrome (passed from parents) - A diagram shows a normal pair of chromosome 21s, and the process of non-disjunction resulting in trisomy 21 down syndrome. ## Inversion ## Translocation ## Deletion ## Duplication - A diagram shows the process of inversion, translocation, deletion, and duplication in chromosomes. ## Balanced (Reciprocal) Translocation ## Unbalanced Translocation ## Inversion ## Deletion ## Duplication - A diagram shows balanced translocation, unbalanced translocation, inversion, deletion, and duplication. ## Thank you! - A picture of a tag attached to three daisies, with the words "Thank you!".