Alterations of chromosome structure Two ways that cells of Eukaryotic organisms divide Mitosis – which provides for growth, tissue repair and asexual reproduction produces daughter cells genetically identical to the parent cell Meiosis- needed for reproduction, yields haploid daughter cells- cells with one member of each homologous chromosome pair Meiosis- occurs repeatedly in our lifetime as our testes and ovaries produce gametes Almost always, the meiotic spindle distributes chromosomes to daughter cells without error Nondisjunction- is an accident in which the members of a chromosome pair fail to separate Nondisjunction in Meiosis I A pair of homologous chromosomes does not separate during meiosis I In this case, all the resulting gametes end up with abnormal number of chromosomes Two of the gametes have three chromosomes, two of which are homologous; the other two gametes have only one chromosome each. Nondisjunction in Meiosis II Meiosis I is normal but one pair of sister chromatids fails to move apart during meiosis II In this case, two of the resulting gametes are abnormal Fertilization after nondisjunction An egg cell with two copies of one of its chromosomes (n+1) is fertilized by a normal sperm cell (n). The resulting zygote has an extra chromosome (2n+1) chromosomes Mitosis will then transmit the abnormality to embryonic cells If this were a real organisms and it survived, it would have an abnormal karyotype and probably a syndrome of disorders caused by the abnormal number of genes Fertilization after nondisjunction Nondisjunction can lead to an abnormal chromosome either sex of any sexually reproducing diploid organisms, including humans For example, there is nondisjunction affecting human chromosomes 21 during meiosis I, half of the resulting gametes will carry an extra chromosome 21 Then if one of these gametes unites with a normal gametes unites with a normal gamete, trisomy 21 will result Nondisjunction in Meiosis Nondisjunction in Meiosis does not affect just autosomes, such as chromosome 21. It can also lead to abnormal number of sex chromosomes, X and Y Klinefelter Syndrome An extra X chromosome in a male making him XXY Occurs approximately in every 2,000 live births Once in every 1,000 male births Men with this disorder have male sex organs, but the testes are abnormally small and the individuals is sterile Klinefelter Syndrome The syndrome often includes breast enlargement and other feminine body contours Klinefelter syndrome is also found in individuals with more than one additional sex chromosomes such as XXYY, XXXY, or XXXXXY These abnormal numbers of sex chromosomes probably result from multiple non disjunctions; such men are more likely to be mentally retarded than XY or XXY individuals Supernumerary Y syndrome Human males with a single extra Y chromosome (XYY) do not have any well-defined syndrome although they tend to be taller than average Appearance of normal male May show some lack of control over impulsive behaviours Usually average intelligence level Triple X Syndrome or Metafemale Females with an extra X chromosome (XXX) They have limited fertility but otherwise apparently normal Turner Syndrome Females who are lacking an X chromosome are designated XO They have a characteristic appearance, including short stature and often a web of skin extending between the neck and shoulders Women with Turner syndrome are sterile because their sex organs do not fully mature at adolescence They have poor development of breasts Usually of normal intelligence I in 5,000babies born (about 1 in 2, 500 female births) The sex chromosome abnormalities described here the crucial role of the Y chromosome in determining a person’s sex. In general, a single Y chromosome is enough to produce “maleness,” even in combination with several X chromosomes. The absence of a Y chromosome results in “femaleness” Alterations of chromosome structure Even if all chromosomes are present in normal numbers abnormalities in chromosome structure may cause disorder Breakage of a chromosome can lead to a variety of rearrangements affecting the genes of that chromosome Deletion If a fragment of a chromosome is lost, the remaining chromosome will then have a deletion. Deletions, especially large ones tend to have the most serious effects One example is a specific deletion in chromosome 5 that causes the cri du chat (“cat-cry”) syndrome Cri du chat Syndrome (5p-) A child born with this syndrome is mentally retarded and has a small head and a cry like the mewing of the cat Death usually occurs in infancy or early childhood Duplication If a fragment from one chromosome joins to a homologous chromosome, it will produce a duplication Inversion If a fragment reattaches to the original chromosomes but in the reverse direction Inversions are less likely than deletions or duplications to produce harmful effects In inversions all genes are still present in their normal number Translocation The attachment of a chromosomal fragment to a non homologous chromosomes Reciprocal translocation –two non homologous chromosomes exchange segments Like inversions, translocations may or may not be harmful Some people with Downsyndrome have only one part of a third chromosome 21, as the result of a translocation, it is attached to another (non homologous chromosome) Chromosomal translocation Chromosomal changes present in sperm or egg can cause congenital disorders, such changes in somatic cell may contribute to the development of cancer For example, chromosomal translocation in somatic cells in the bone marrow is associated with chronic myelogenous leukemia (CML) CML is the most common of the leukemias Chromosomal translocation The cancers affecting cells that give rise to white blood cells (leukocytes) In the cancerous cells of most CML patients, a part of chromosome 22 has switched places with a small fragment from chromosome 9 This reciprocal translocation activates a gene that leads to leukemia The chromosomes ending up with the activated cancer-causing gene is called the “ Philadelphia chromosome” after the city where it was discovered
