Inherited pericentric inversion of chromosome number two: A linkage study*

Abstract

Pericentric inversion has been suggested as one possible explanation for an abnormally located, human somatic cell autosomal centromere in twenty-one instances (reviewed in Jacobs et al. 1967; see also Summitt & Atnip, 1966; Nance & Engel, 1967; Schmid, 1967; and Soudek, Laxovh & AdBmek, 1968).Five of these cases involved chromosome no.2: three were found in individuals with various abnormalities (mild mental retardation and multiple congenital anomalies, DeGrouchy et al. 1963 ; mild mental retardation and hypogonadism, Miller, 1966, cited in Cohen, 1967; severe mental retardation and features of the de Lange syndrome, Breg, 1966, cited in Cohen, 1967) and two in normal individuals (Carr, 1962; Summitt & Atnip, 1966).Summitt and Atnip also reported that the abnormal no. 2 chromosome occurred in the normal mother of the propositus and in two of her five normal siblings.In this paper we report the occurrence, inheritance, segregation and genetic linkage relations of an abnormal number 2 chromosome.The most likely explanation for the abnormality is that it results from an asymmetric pericentric inversion, although formal proof of this is lacking.This is the &st report of a study in which a cytologically recognizable abnormality of the number 2 chromosome was used to determine whether any one of the genetic loci controlling a number of serum proteins, red cell enzymes and red cell antigens is located on this chromosome. METHODSThe proposita (kindred no.10854) was identified during a routine cytologic examination to determine sex in a case of what was subsequently identified as adrenogenital syndrome.Karyotyping was done by direct microscopical observation of peripheral blood leukocytes cultured in Medium 1A (Grand Island Biological Co., Grand Island, New York) and harvested using a modification of the technique of Moorehead et a1 (1960).The red cell enzymes, adenylate b a s e (AK), 6-phosphogluconate dehydrogenase (6-PGD), lactic dehydrogenase (LDH), malic dehydrogenase (MDH), phosphoglucomutase (PGM) and acid phosphatase (AP), were in each case separated by vertical starch gel electrophoresis (Electrostarch, Electrostarch Co., Madison, Wisconsin) at pH 7.0 using a discontinuous buffer system (gel buffer 0 .0 0 5 ~ histidine, bridge buffer 0 .4 1 ~ citric acid: both adjusted to pH 7.0 with sodium hydroxide).Gels which are developed for 6-PGD had 25 mg NADP added per litre of cooked gel.Electrophoresis at 10 V/cm.was continued for 6 5 hr. in the gels which were developed for AK, 6-PGD, LDH and MDH and for 20-24 hr. in the gels which were developed for PGM and AP.Bands of enzymic activity were then visualized using an 0.75 yo agar gel overlay and the customary reagents for histochemical detection.Red cell antigen and * Supported in part by the U.S.