(deficiency) n. (in genetics) a type of mutation involving the loss of DNA. The deletion may be small, affecting only a portion of a single gene, or large, resulting in loss of a part of a chromosome and affecting many genes.
Sometimes during cell division chromosomes may be lost or duplicated, or abnormalities in the structure of individual chromosomes may occur. The surprising fact is the infrequency of such errors. About one in 200 live-born babies has an abnormality of development caused by a chromosome, and two-thirds of these involve the sex chromosomes. There is little doubt that the frequency of these abnormalities in the early embryo is much higher, but because of the serious nature of the defect, early spontaneous ABORTION occurs.
Chromosome studies on such early abortions show that half have chromosome abnormalities, with errors of autosomes being three times as common as sex chromosome anomalies. Two of the most common abnormalities in such fetuses are triploidy with 69 chromosomes and trisomy of chromosome 16. These two anomalies almost always cause spontaneous abortion. Abnormalities of chromosome structure may arise because of:
Deletion Where a segment of a chromosome is lost.
Inversion Where a segment of a chromosome becomes detached and re-attached the other way around. GENES will then appear in the wrong order and thus will not correspond with their opposite numbers on homologous chromosomes.
Duplication Where a segment of a chromosome is included twice over. One chromosome will have too little nuclear material and one too much. The individual inheriting too little may be non-viable and the one with too much may be abnormal.
Translocation Where chromosomes of different pairs exchange segments.
Errors in division of centromere Sometimes the centromere divides transversely instead of longitudinally. If the centromere is not central, one of the daughter chromosomes will arise from the two short arms of the parent chromosome and the other from the two long arms. These abnormal daughter chromosomes are called isochromosomes.
These changes have important bearings on heredity, as the e?ect of a gene depends not only upon its nature but also upon its position on the chromosome with reference to other genes. Genes do not act in isolation but against the background of other genes. Each gene normally has its own position on the chromosome, and this corresponds precisely with the positon of its allele on the homologous chromosome of the pair. Each member of a pair of chromosomes will normally carry precisely the same number of genes in exactly the same order. Characteristic clinical syndromes, due to abnormalities of chromosome structure, are less constant than those due to loss or gain of a complete chromosome. This is because the degree of deletion, inversion and duplication is inconstant. However, translocation between chromosomes 15 and 21 of the parent is associated with a familial form of mongolism (see DOWN’S (DOWN) SYNDROME) in the o?spring, and deletion of part of an X chromosome may result in TURNER’S SYNDROME.
Non-disjunction Whilst alterations in the structure of chromosomes arise as a result of deletion or translocation, alterations in the number of chromosomes usually arise as a result of non-disjunction occurring during maturation of the parental gametes (germ cells). The two chromosomes of each pair (homologous chromosomes) may fail to come together at the beginning of meiosis and continue to lie free. If one chromosome then passes to each pole of the spindle, normal gametes may result; but if both chromosomes pass to one pole and neither to the other, two kinds of abnormal gametes will be produced. One kind of gamete will contain both chromosomes of the pair, and the other gamete will contain neither. Whilst this results in serious disease when the autosomes are involved, the loss or gain of sex chromosomes seems to be well tolerated. The loss of an autosome is incompatible with life and the malformation produced by a gain of an autosome is proportional to the size of the extra chromosome carried.
Only a few instances of a gain of an autosome are known. An additional chromosome 21 (one of the smallest autosomes) results in mongolism, and trisomy of chromosome 13 and 18 is associated with severe mental, skeletal and congenital cardiac defects. Diseases resulting from a gain of a sex chromosome are not as severe. A normal ovum contains 22 autosomes and an X sex chromosome. A normal sperm contains 22 autosomes and either an X or a Y sex chromosome. Thus, as a result of nondisjunction of the X chromosome at the ?rst meiotic division during the formation of female gametes, the ovum may contain two X chromosomes or none at all, whilst in the male the sperm may contain both X and Y chromosomes (XY) or none at all. (See also CHROMOSOMES; GENES.)... sex chromosomes
Patients with Turner’s syndrome may require therapeutic help throughout their life. In early childhood this may revolve around surgical correction of cardiovascular disease and treatment to improve growth. Usually, PUBERTY will need to be induced with oestrogen therapy (see OESTROGENS). In adult life, problems of oestrogen therapy, prevention of osteoporosis (see under BONE, DISORDERS OF), assessment and treatment of HYPERTENSION and assisted fertility predominate. For the address of the UK Turner Syndrome Society, see Appendix 2.... turner’s syndrome
Health Encyclopedia