RARE VARIANTS IN MICRONESIANS 267 per 1.200 variants for each system, and the wznweighted average of all the systems, emploved to prevent an extensive study of a single system from dominating the picture. By this approach, the average frequency with which variants are encountered in the systems under consideration, on the basis of 21,180 determinations, is 11.000 observations. Reports on the frequency of rare variants in a variety of populations are accumulating rapidly. For instance. among South American Indians, we find, based on ADA. AKi, ICDs, LDH, MDHs. PEPA. PEPB, PGM,, PGM:, 6PGD, PHI, Alb, Cp, Hb A, and Tf of table 1, an unweighted rare variant frequency of 3.2/1,000 determinations [2]. On the other hand, among Caucasians living in the British Isles, Western Europe, and the United States. a study of ADA, AK,, CA;, ICD; LDH, MDH: NP, PEPA, PEFB, PGM,, PGM:,, 6PGD, PHI, TPI, Cp, Hb A, and Tf of table 1 reveals an unweighted variant frequency of 2.91000 [6, 21-25]. This latter gure is greatly influenced bythe relatively high frequency of ceruloplasmin varian:s in the two small series on Caucasians [22, 23]. Since the samples of Micronesians and South American Indians contain manyrelatives and the West European sample does not, the usual (x7) contrast is inappropriate. Caution in this contrast is also indicated because the mix of systems varies according to the population, the dividing line between “‘rare’’ and polymorphicis arbitrary, and the determinations originate in a variety of laboratories. Taken simply at face value, however, the samples of Micronesians and South American Indians difier by a factor of three in the frequency of rare variants: we suspect this is a biologically meaningful difierexce. The frequency of such rare variants is determined by a complex interplay between mutation, selection, and random loss: the latter is highly related to population structure (26, 27]. Assuming for the moment the validity of the observed difierer.ce between Micronesians and Amerindians, both the data and our knowl- edge o7 these populations are still insufficient to permit conclusions concerning the factors responsible for the difference. However, we believe that there will be situations wherein differences exist, and the populations are more appropriately matched and sampled, as in studies on Jananese and English, for which it may be possible to reach valid inferences concerning the factors responsible for the difference [28]. " SUMNARY Blood specimens from a sample of 373 Marshall Islanders were studied with reference to variants of 23 serum proteins and erythrocyte enzymes. Six of the traits studied exhibited genetic polymorphisms (adenosine deaminase. phosphoglucom:=tase;. acid phosphatase, 6-phosphogiuconate dehydrozenase, haptoglobin, and group specific component). There were in addition four “rare” variants (albumin. transferrin, lactate dehydrogenase, and salactose-1-phosphate uridvlyltransferase) involving nine persons, among 8.503 determinations. The frequency of rare variants in Micronesians was compared with the frequencies in West European Caucasians and Amerindians. There are manydifficulties in such comparisons. and althourh the observed values for the three ethnic groups differ by a factor of three