Clinical genetics / edited by Arnold Sorsby.

Date:
1953
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Clinical genetics / edited by Arnold Sorsby. Source: Wellcome Collection.

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    EVALUATION OF LINKAGE Sìb-paìr method Penrose, in 1935, first showed that it is possible to deduce linkage between characters on the autosomes by examining numbers of pairs of siblings all of one generation without knowledge of their parental characteristics, and this technique has the very great advantage that by it large numbers of family groups, such as school children, can be examined. The principle of the technique is that if linkage exists between two conditions, then examination of large numbers of pairs of siblings with respect to these conditions reveals that there is a greater number of cases in which the sibs are similar in both characters, or dissimilar in both, than there are cases in which the sibs are similar in respect to one character and dissimilar in respect to the other. This principle can be simply illustrated as follows. If there are n children in a family, then the number of sib-pairs that can be studied is Thus a family of 4 children represents 6 sib-pairs. If 2 characters, P and Q, are studied in these children, then each sib-pair will fall into one or other of four categories; (1) the pair is similar with respect to both characters. This group we shall describe as similar-similar (S.S.). (2) Both children are alike with respect to character P, but they differ with respect to character Q. This group is similar-dissimilar (S.D.). (3) The children are unhke with respect to character P, but аИке with respect to Q. This group is dissimilar- similar (D.S.). (4) The children are dissimilar in respect of both P and Q. They are in the category dissimilar-dissimilar (D.D). After all the sib-pairs have been allocated to one or other category, the totals of the groups S.S., S.D., D.S., and D.D. are noted, and linkage can be suspected if the product of S.S. and D.D. exceeds that of S.D. and D.S. It is then necessary to apply the standard statistical test of significance to the figures to determine the probability that the two conditions are associated by chance. A probabihty of under 0-05 is usually taken as possibly indicating Unkage, and linkage can be definitely established if the J} test indicates a probabihty of 0-01 or less. The value of is determined by the formula ^^2 _ n(S.S. X D.D. - S.D. X D.S.)2 ~ (S.S. + S.dT) (d.s. + d.d.) (S.S. + d.S.) (S.d. + d.d.) A typical example of the demonstration by this technique of linkage between two characteristics is shown in the Table, adapted from Taillard (1951). In this case, sib-pairs, totalling 171 pairs, from 20 families have been studied with regard to the incidence of two characteristics of the ear: (1) the manner by which the ear is attached to the skull, whether it is fiat or whether projecting from the head, and (2) the fashion of attachment of the lobe of the ear : whether it is completely free or whether it is attached to the skin of the cheek at the angle of the jaw. The Table shows the incidence of similar and dissimilar pairs in each family with the totals in each category, and has been calculated according to the above formula. Its value of 9-55 indicates a probability of 0-001 (derived from standard statistical Tables) which means that there is only 1 chance in 1,000 that the associa¬ tion of these two characteristics so frequently could be due to chance. 70