GENOMIC ORGANIZATION, SEQUENCE AND POLYMORPHISM OF THE HUMAN CHROMOSOME-4-SPECIFIC ALPHA-SATELLITE DNA

Two alpha-satellite fragments specific for human chromosome 4 have bee n cloned and characterized. Under stringent annealing conditions, they hybridized in situ only to the pericentromeric region of chromosome 4 , but under non-stringent conditions they hybridized to all chromosome s containing the sequences of alpha-satellite suprachromosomal family 2 (viz., chromosomes 2, 4, 8, 9, 13, 14, 15, 18, 20, 21 and 22). South ern blot analysis reveals the 3.2-kb higher-order repeated unit which exists in two forms: as a single MspI fragment or a combination of the 2.6-kb and 0.6-kb MspI fragments. The two chromosome-4-specific clone d sequences appear to be different parts of this repeated unit. Taken together they constitute about 60% of its length. The primary structur e of the higher-order repeated unit is characterized by a dimeric peri odicity of the D1-D2 type which is usual to suprachromosomal family 2. At least in one site this regularity is disrupted by monomer deletion leading to the D2-D2 monomeric order. The most likely mechanism of th is monomer excision is homologous unequal crossing-over. These sequenc es may serve as both cytogenetic and restriction-fragment length polym orphism (RFLP) markers for the pericentromeric region of chromosome 4.