Structural Changes in Chromosomes

Abstract

Chromosomes can be structurally identified by their sizes, positions of centromeres and nucleolar organizers, and patterns of chromomeres, heterochromatin, and bands. There are four types of aberrations in the chromosomal structure such as deletions, duplications, inversions, and translocations which can be detected cytologically under the microscope. Some changes are however too subtle to be detected cytologically. Deletions represent missing segments of chromosomes. The homozygous deletions can be lethal, whereas heterozygous deletions can be nonlethal or lethal and can express recessive genes uncovered by deletion. Duplications can cause an imbalance in the genetic material, thereby producing phenotypic effect in the organism and leading to increased variety of gene functions. Inversions are caused by 180 degree turn of a segment of a chromosome, which cause little problem for an organism under homozygous condition, but inversion heterozygotes often have pairing difficulties during meiosis, leading to formation of inversion loops. Crossing over within loops usually results in inviable products. The crossover products will be different for pericentric and paracentric inversions. Translocations involve relocation of a chromosomal segment to another position in the genome. In heterozygous state, the translocations produce duplication-deletion meiotic products, which can lead to unbalanced zygotes, and new gene linkages. Chromosome rearrangements can cause ill health in human population – infertility and mental retardation being the dominant effects.

Glossary

Adjacent 1 segregation

 Adjacent nonhomologous centromeres move to the same pole. This results in an unbalanced chromosomal complement that will result in a zygote with partial trisomy of one chromosome and partial monosomy of the other when fertilized by a normal haploid gamete. This segregation pattern often is compatible with viability.

Adjacent 2 segregation

 Adjacent homologous centromeres move to the same pole; this usually results in large amounts of unbalanced chromatin, which is usually incompatible with embryonic survival.

Allele

 One of the possible mutational states of a gene, distinguished from other alleles by phenotypic effects.

Alternate segregation

 It is an example of balance segregation in which both normal homologues move to one pole and translocation homologues move to another pole.

Anal atresia

 Anal atresia is an imperforate anus. In anal atresia, the tissue closing the anus may be several centimeters thick or just a thin membrane of skin.

Angelman syndrome

 A rare congenital disorder characterized by mental disability and a tendency to jerky movement, caused by the absence of certain genes normally present on the copy of chromosome 15 inherited from the mother.

Balanced translocation

 Balanced translocations are the one with an even exchange of material and with no extra or missing genetic information. These translocations have full functionality. The unbalanced translocations are the ones in exchange of chromosome material which is unequal resulting in extra or missing genes.

Beckwith-Wiedemann syndrome

 Beckwith-Wiedemann syndrome is an overgrowth disorder usually present at birth. It can also cause child behavior problems. Common features are large tongue, above average birth weight and length, midline abdominal wall, ear creases or ear pits, and low blood sugar after birth.

Chromosomal aberration

 Any change resulting in the duplication, deletion, or rearrangement of chromosomal material. Abnormal structure or number of chromosomes includes deficiency, duplication, inversion, translocation, aneuploidy, polyploidy, or any other change from the normal pattern.

Chronic myelogenous leukemia

 Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that starts in the blood-forming cells of the bone marrow and invades the blood.

Coloboma

 A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc.

Cri-du-chat syndrome

 Cri-du-chat (cat’s cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also 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.

Crossing over

 The exchange of chromosomal material (parts of chromosomal arms) between homologous chromosomes by breakage and reunion. The exchange of material between nonsister chromatids during meiosis is the bases of genetic recombination.

Deficiency (deletion)

 A chromosomal mutation involving the loss or deletion of chromosomal material. Deficiency heterozygotes are hemizygous for the genes located in the deleted segment; many deficiencies produce genetic effects similar to gene mutations. Deletion also occurs when a block of one or more nucleotide pairs is lost from a DNA molecule.

Dicentric chromosome

 It is an abnormal chromosome with two centromeres. It is formed through the fusion of two chromosome segments, each with a centromere, resulting in the loss of acentric fragments and the formation of dicentric fragments.

Disjunction

 An act of disjoining.

Down syndrome

 An abnormal human phenotype including mental retardation, due to a trisomy of chromosome 21; more common in babies born to older mothers.

Duplication

 Gene duplication or chromosomal duplication involves duplication of a region of DNA that contains a gene.

Follicular lymphoma

 Follicular lymphoma is a type of non-Hodgkin lymphoma. It develops when the body makes abnormal B lymphocytes – the lymphoma cells. (B lymphocytes are white blood cells that fight infection). The lymphoma cells build up in lymph nodes. The most common symptom is a painless swelling in the neck, armpit, or groin.

Genetic imbalance

 It is to describe situation when the genome of a cell or organism has more copies of some genes than other genes due to chromosomal rearrangements or aneuploidy.

Heterozygous

 A diploid organism is heterozygous at a gene locus when its cells contain two different alleles of a gene. The cell or organism is called a heterozygote specifically for the allele in question; therefore, heterozygosity refers to a specific genotype.

Homologous

 Chromosomes that occur in pairs and are generally similar in size and shape, one having come from the male parent and the other from the female parent. Such chromosomes contain the same array of genes.

Homologous centromeres

 During meiosis, homologous chromosomes pair and then segregate from each other at the first meiotic division. Homologous centromeres appear to be aligned when chromosomes are paired.

Hyperphagia

 An abnormally great desire for food; excessive eating.

Hyperplastic genitalia

 Underdeveloped or incompletely developed genitalia.

Inversion

 Rotation of a segment of a chromosome by 180° so that the genes in this segment are present in the reverse order; characteristic inversion loops are produced during meiosis in the inversion heterozygotes.

Interstitial deletion

 Deletion that does not involve the terminal parts of a chromosome.

Klinefelter’s syndrome

 Sterile human males with the XXY chromosome constitution; other associated symptoms as well.

Linkage analysis

 It is the study aimed at establishing linkage between genes. It is the tendency for genes and other genetic markers to be inherited together because of their location near one another on the same chromosome. Linkage analysis is used for gene hunting and genetic testing.

Mental retardation

 It is a condition diagnosed before age 18, usually in infancy or prior to birth that includes below-average general intellectual function and a lack of the skills necessary for daily living.

Microcephaly

 Abnormal smallness of the head, a congenital condition associated with incomplete brain development. It is a rare neurological condition in which an infant’s head is significantly smaller than the heads of other children of the same age and sex. Sometimes detected at birth, microcephaly usually is the result of the brain developing abnormally in the womb or not growing as it should after birth. Microcephaly can be caused by a variety of genetic and environmental factors.

Microdeletion syndrome

 Microdeletion syndrome is a syndrome caused by a chromosomal deletion (<5 Mb) spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping (2–5 Mb).^{[ 1 ][ 2 ]} Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.

Microduplication syndrome

 Microduplications, or submicroscopic duplications, are chromosomal duplications that are too small to be detected by light microscopy using conventional cytogenetics methods. Specialized testing is needed to identify these duplications. 1q21.1 duplication syndrome or 1q21.1 (recurrent) microduplication is a rare aberration of chromosome 1.

Mongolism

 It is a congenital disorder caused by having an extra 21st chromosome; results in a flat face and short stature and mental retardation.

Noncrossover chromatids

 Crossing over, or recombination, is the exchange of chromosome segments between nonsister chromatids in meiosis. Crossing over creates new combinations of genes in the gametes that are not found in either parent, contributing to genetic diversity. The chromatids of two homologous chromosomes are called nonsister chromatids.

Paracentric inversion

 A reversal of the normal order of genes in a chromosome segment involving only the part of a chromosome at one side of the centromere.

Pericentric inversion

 A reversal of the normal order of genes in a chromosome segment involving parts of a chromosome at both sides of the centromere.

Prader-Willi syndrome

 It is a rare congenital disorder characterized by learning difficulties, growth abnormalities, and obsessive eating, caused especially by the absence of certain genes normally present on the copy of chromosome 15 inherited from the father.

Proto-oncogene

 These genes code for proteins that help regulate cell growth. These important genes are called proto-oncogenes. A change in the DNA sequence of the proto-oncogene gives rise to an oncogene, which produces a different protein and interferes with normal cell regulation.

Pseudodominance

 It is the situation in which the inheritance of a recessive trait mimics a dominant pattern.

Reciprocal translocation

 Reciprocal translocations are usually an exchange of material between nonhomologous chromosomes.

Recombinant frequency

 When two genes are located on the same chromosome, the chance of a crossover producing recombination between the genes is related to the distance between the two genes. Thus, the use of recombination frequencies has been used to develop linkage maps or genetic maps.

Recombination

 The process by which offspring derive a combination of genes different from that of either parent; the generation of new allelic combinations. In higher organisms, this can occur by crossing over.

Ring chromosome

 A ring chromosome is a chromosome whose arms have fused together to form a ring. A ring chromosome is denoted by the symbol r in human genetics or R in Drosophila genetics.

Robertsonian translocation

 Translocation arising from breaks at or near the centromeres of two acrocentric chromosomes. The reciprocal exchange of broken parts generates one large metacentric chromosome and one very small chromosome.

Seizure

 A seizure is a sudden surge of electrical activity in the brain. A seizure usually affects how a person appears or acts for a short time.

Syndrome

 A group of symptoms that occur together and represent a particular disease.

Tandem

 The occurrence of two identical sequences, one following the other, in a chromosome segment.

Terminal tandem repeats

 Tandem repeats of nucleotide sequences reaching the extreme terminus of the chromosome.

Translocation

 Change in position of a segment of a chromosome to another part of the same chromosome or to a different chromosome.

Turner’s syndrome

 In human beings; individuals having XO chromosome constitution, being phenotypically female, but having rudimentary sexual organs and mammary glands.

Unbalanced genetic rearrangement

 Chromosome structure abnormalities can be either unbalanced rearrangements or balanced rearrangements. The various unbalanced rearrangements involve deletion, duplication, or both. Deletion of a chromosome segment leads to partial monosomy of that segment. Duplication of a chromosome segment leads to partial trisomy of that segment. Any mutation leading to an imbalance like monosomy, trisomy, or others can result in an abnormal phenotype.

Viability

 It is the ability of a living organism to maintain itself or recover its potentialities.

Zygotic mortality

 A form of reproductive isolation in which fertilization occurs but development stops soon after preventing much of the warm blood from reaching the surface of the body, where heat could be lost.