Polyploidy. When there is one extra complete set, to give 69 chromosomes in total, then this is known as triploidy

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Chromosome disorders (Numerical abnormalities)

When cells carry complete extra sets of chromosomes, this is called polyploidy. When there is one extra complete set, to give 69 chromosomes in total, then this is known as triploidy. Two extra sets of chromosomes, to give 92 chromosomes in total, would be called tetraploidy.

When individual whole chromosomes are missing or extra, this is called aneuploidy. This can happen with any of the autosomal chromosomes (1 to 22) or the sex chromosome (X or Y).

If one extra complete chromosome is present, this is known as trisomy and the number of chromosomes in each affected cell would be 47. The most common disorder arising from a trisomy is Down's syndrome (Trisomy 21). Two extra complete chromosomes would be called tetrasomy and the number of chromosomes would be 48. If a complete chromosome is missing, this is known as monosomy and the number of chromosomes in each cell would be 45.

Down's syndrome (Trisomy 21)

Because chromosomes are the packages of genetic information and contain all of our genes or instructions, people with Down syndrome actually have three copies of all of the genes located on chromosome 21. It is estimated that there are 400 genes on chromosome 21. Mosaic Down syndrome is a developmental disability caused by an extra chromosome. The difference is the same as in Down syndrome, except that individuals with Mosaic Down syndrome do not have the extra chromosome on every cell. trisomy is the result of a misdivision in the sperm or the egg We do not know what causes a trisomy to occur.

When the women get older, the risk for having a pregnancy with a trisomy increases. In fact, 80% of babies born with Down syndrome are born to women younger than 35. Overall, the likelihood of a woman under age 30 giving birth to a child with Down syndrome is less than 1:1000 and about 1:112 at 40 years of age. While we tend to focus on trisomy 21 because it is the most common trisomy.

Trisomy 18 (Edwards syndrome)

Trisomy 18 is a rare condition that occurs in approximately 1 in 6,000 live births which makes it about ten times rarer that Down syndrome. 95% of trisomy 18 is caused by an extra number 18 chromosome and 5% is due to a translocation involving chromosome 18. Majority of infants with trisomy 18 will have a heart defect and these infants can also have kidney defects, lung and diaphragm abnormalities. Because of their severe physical birth defects about 90% of infants with trisomy 18 will die in the first days of life. Those infants that do survive, have profound mental retardation. Most do not survive beyond the first few months of life, but some children do survive until adolescence.

Trisomy 13 (Patau syndrome)

Trisomy 13 (Patau syndrome) is the third most common autosomal abnormality among live births after Down syndrome (trisomy 21) and Edwards syndrome (trisomy 18). Trisomy 13 occurs in about 1 out of every 10,000 newborns.

Children with trisomy 13 can have cleft lip and palates, extra fingers and toes, malformed and rotated internal organs, severe congenital heart defects and severe brain abnormalities.

47,XXY syndrome (Klinefelter syndrome)

Klinefelter syndrome, 47,XXY or XXY syndrome, is a condition caused by a and extra X chromsomes and it occurs in about 1 in 500 males (therefore 1 in 1000 births). Affected individuals have two X chromosomes and one Y chromosome. Many individuals are unaware that they have Klinefelter syndrome as the differences due to having an extra X chromosome are not very obvious and often go undetected. The main problems seen in Klinefelter syndrome are small testicles and reduced fertility.

47,XYY Males

About 1 in 1,000 boys are born with an extra Y chromosome and have a 47,XYY karyotype. Most often, this extra Y chromosome causes no unusual physical features or medical problems. Males with 47,XYY syndrome can sometimes be taller than average and may have an increased risk of learning disabilities and delayed speech and language skills. Developmental delays and behavioral problems are also possible, but these characteristics vary widely among affected boys and men. Most males with 47,XYY syndrome have normal sexual development and are able to conceive children.

47,XXX (triplo-X, trisomy X, and XXX syndrome)

About 1 in 1000 girls are born with Triple X syndrome. Triple X syndrome often has no associated physical features or medical problems. A small proportion of women with the condition may have menstrual irregularities and can have learning disabilities, delayed speech, and language skills. Many individuals with 47,XXX syndrome have completely normal physical and mental development. Triple X syndrome is not inherited, but usually occurs as an event during the formation of reproductive cells (ovum and sperm). An error in cell division called nondisjunction can result in reproductive cells with additional chromosomes.

Trisomy 16

Trisomy 16 is the most common autosomal trisomy seen in miscarriages and accounts for at least 15% of first trimester miscarriages. Most pregnancies with trisomy 16 are lost around 12 weeks although a small percent may be lost in the second trimester. A few fetuses with mosaic trisomy 16 have survived until birth. Most of these infants have growth failure, psychomotor retardation and die in infancy.

Trisomy 22

Complete trisomy 22 is the second most common finding in miscarriages after trisomy 16. Survival beyond the first trimester of pregnancy is rare. Complete trisomy 22 is very rare. Most affected individuals with complete trisomy 22 die before or shortly after birth due to severe birth defects.

Turner Syndrome

X-Chromosome Monosomy

Turner syndrome is a disorder caused by the loss of genetic material from one of the sex chromosomes. During the process in which oocytes (eggs) or sperm are formed, one of the sex chromosomes is sometimes "lost". An embryo receiving only a Y-chromosome can not survive, but an embryo receiving only a X-chromosome may survive and develop as a female with Turner syndrome. The karyotype of X-monosomy is termed, "45X" meaning that an individual has 44 autosomes and a single X-chromosome. The usual female karyotype is 46, XX.

X-Chromosome Mosaicism

A sex chromosome may also be lost during early stages of embryonic development, such that some cells of the growing body receive a single X chromosome. This condition is called mosaicism, and the clinical features of Turner syndrome correlate with the relative percentage of 45X cells within the body.

X-Chromosome Defects

A third cause of Turner syndrome involves X-chromosome defects rather than complete loss. For example, one X-chromosome may be fragmented, have portions deleted or other structural problems such as ring formation preventing the normal expression of X-chromosome genes.

The clinical consequences of having one normal and one structurally defective X-chromosome vary widely. A small deletion may result in a single feature such as ovarian failure or short stature and no other effects. Larger deletions or deletions affecting critical areas regulating the whole chromosome may result in a full spectrum of Turner syndrome problems.

Structural abnormalities:

Changes that affect the structure of chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many genes along the chromosome and disrupt the proteins made from those genes.

Structural changes can occur during the formation of egg or sperm cells, in early fetal development, or in any cell after birth. Pieces of DNA can be rearranged within one chromosome or transferred between two or more chromosomes. The effects of structural changes depend on their size and location, and whether any genetic material is gained or lost.  Some changes cause medical problems, while others may have no effect on a person’s health.

Deletions: A deletion (sometimes called a partial monosomy) involves loss of a segment of a chromosome. Deletions can occur near to the centromere (proximal deletion), in the middle of a chromosome arm (interstitial deletion), at the end of the chromosome (terminal deletion) or as a tiny segment missing very near to the telomere (subtelomeric deletion). Small deletions are less likely to be fatal; large deletions are usually fatal - there are always variations based on which genes are lost.

Duplications: A duplication (sometimes called a partial trisomy) occurs when an extra copy of a segment of a chromosome is present. If a person has two extra copies of a chromosomal segment, this is known as a triplication (or sometimes as a partial tetrasomy). Duplications and triplications can cause symptoms due to gain of extra copies of any genes contained within the additional chromosomal segment. Duplications arise from an event termed unequal crossing-over that occurs during meiosis between misaligned homologous chromosomes. Duplications of oncogenes are a common cause of many types of cancer, as in the case breast cancer.

Translocations: A portion of one chromosome is transferred to another chromosome. a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. Several forms of cancer are caused by acquired translocations such as leukemia (acute myelogenous leukemia and chronic myelogenous leukemia). This is due to a mis-segregation (Nondisjunction) during gametogenesis.There are two main types of translocations:

    1. Reciprocal translocation: Segments from two different chromosomes have been exchanged, Reciprocal translocations are the most common type of translocation.

    2. Robertsonian translocation: two acrocentric chromosomes fuse near the centromere region with loss of the short arms

Inversions: Inversions arise when a chromosome breaks in two places, the intervening segment flips around and is then re-inserted into the 'gap. An inversion that involves the chromosome’s constriction point (centromere) is called a pericentric inversion.  An inversion that occurs in the long (q) arm or short (p) arm and does not involve the centromere is called a paracentric inversion. Inversions would not usually cause symptoms in the carrier but can lead to fertility problems.

Insertions: A portion of one chromosome has been removed from its normal place and inserted into another chromosome. An insertion (also called an insertion mutation) is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping. Insertions can be anywhere in size from one base pair incorrectly inserted into a DNA sequence to a section of one chromosome inserted into another.

On a chromosome level, an insertion refers to the insertion of a larger sequence into a chromosome. This can happen due to unequal crossover during meiosis.

  1. N region addition is the addition of non-coded nucleotides during recombination by terminal deoxynucleotidyl transferase.

  2. P nucleotide insertion is the insertion of palindromic sequences encoded by the ends of the recombining gene segments.

Insertions can be particularly hazardous if they occur in an exon, the amino acid coding region of a gene.

Rings: Ring chromosomes arise when the ends of both arms of a chromosome are lost and the remaining broken ends join together to form a ring shape. Ring chromosomes may form in cells following genetic damage by mutagens like radiation, but they may also arise spontaneously during development. Ring formation of an X-chromosome causes Turner syndrome.

An isochromosome is a chromosome with two identical arms.  Instead of one long (q) arm and one short (p) arm, an isochromosome has two long arms or two short arms.  As a result, these abnormal chromosomes have an extra copy of some genes and are missing copies of other genes.

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