Chromosomal Disorders

Down Syndrome - Caused by an extra copy of human chromosome 21

Muscular dystrophy can be caused by the breakage and relocation of a segment of the human X chromosome

Triplet repeat expansion mutations in a gene causing abnormal protein product (Huntington’s disease), sickle-cell anaemia (single bp substitution)

23

22

A karyotype is a display of chromosomes paired according to their size, location of the centromere, and staining patterns

Amniocentesis uses a needle to extract amniotic fluid from the uterus of a pregnant woman from the 14th to 17th week of pregnancy

Chorionic villus sampling

Mitosis is stimulated then arrested in metaphase (form sister chromatids) During mitosis the pairs of chromosomes condense and become visible under a light microscope The condensed chromosomes are then stained with Giemsa dye The dye stains areas of the chromosome rich in Adenine and Thymine base pairs, producing characteristic dark bands Staining the chromosomes results in a smear which is then photographed From analysis of the length of chromosomes, bands and location of centromeres, a karyotype can be assembled In a normal case, there will be 46 chromosomes I.e. 23 pairs Study of a karyotype can determine whether an adult’s chromosomes contain an abnormality which could be passed on. Karyotypes can be useful for determining the possible cause of infertilty or miscarriage Karyotyping is also a good test for chromosomal abnormality in a foetus or identifying the cause of a baby’s birth defects

First, the total number of chromosomes Next, the sex chromosomes Then any extra or missing autosomal chromosomes Examples: 46, XX is female with a normal number of chromosomes 47, XY +18 is male, and has an extra autosomal chromosome 18 46, XY del (7q) is male missing part of long arm of chromosome 7

Euploidy refers to a normal set of chromosomes (i.e. 23 pairs, 2n)

Polyploidy refers to one or more extra sets of the entire genome (3n, 4n etc) Polyploidy does not exist in humans Polyploids can be nearly normal phenotypically. Maybe this is because the normal genetic ratio (or balance) is maintained when there is an entire extra set. One more or one less chromosome disrupts genetic balance far more than does an entire extra set of chromosomes.

Aneuploidy refers to an abnormal chromosome number

Nondisjunction occurs when members of a pair of homologous chromosomes do not move apart properly during meiosis I or fail to separate during meiosis II In both cases of meiotic error gametes with abnormal chromosome number will be produced One gamete will receive 2 copies of the same chromosome The other gamete will receive no copy

If a chromosome is present in triplicate in a cell the cell is trisomic for that chromosome.

If a chromosome is missing from a cell, the cell is said to be monosomic for that chromosome.

Down syndrome (Trisomy 21) Patau syndrome (Trisomy 13) Edward syndrome (Trisomy 18) Syndromes related to sex chromosomes

1866

1 in 700

90% of these are due to nondisjunction during meiosis I in the oocyte; the other 10% are due to nondisjunction in meiosis I or II in males. Although chromosome 21 one of the smallest chromosomes, trisomy 21 severely effects the individual’s phenotype

characteristic facial features, short stature, epicanthal folds, mental retardation

Susceptibility to heart defects, leukaemia and Alzheimer’s disease Most Down syndrome individuals are sexually underdeveloped and sterile. Although there is generally a shorter lifespan, some do live to middle age Frequency of Down Syndrome increases with the age of the mother, from the age of about 30 onwards.

Patau Syndrome

Very rare occurring in only 1 in 15,000 live births. Most cases die in utero. The survival rate of Patau syndrome individuals is low. 50% of live births die within 1 month; most do not survive longer than 6 months