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Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11p13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as well as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.

Human gene mapping would be greatly facilitated if marker loci with sufficient polymorphism information content were generally available. As a source of such markers, we have used cosmids from a human genomic library. We have used a rapid method for screening random cosmids to identify those homologous to genomic regions especially rich in restriction fragment length polymorphisms (Litt and White 1985). This method allows whole cosmids to be used as probes against Southern transfers of genomic DNA; regions of cosmid probes homologous to repeated genomic sequences are rendered unable to anneal with Southern transfers by prehybridization of the probes with a vast excess of non-radioactive genomic DNA. From one cosmid (C1-11) identified by this procedure, we have isolated four single-copy probes, each of which identifies a polymorphic locus. Despite the existence of some linkage disequilibrium in this system, the polymorphism information content was computed as 0.73. Using a somatic cell hybrid mapping panel, we have mapped probes from cosmid 1-11 to human chromosome 12q. Additionally, in situ hybridization of the whole cosmid to metaphase spreads allowed more precise assignment of the locus to the region 12cen----q13. The locus revealed by probes from cosmid 1-11 has been designated D12S6.

A flow sorted chromosome 16-enriched recombinant library was produced to isolate DNA probes useful for constructing a linkage map of 16p, primarily for the study of adult polycystic kidney disease (APKD). The APKD locus has been mapped to chromosome 16 by linkage with the probe 3'HVR, which is located in the region 16p12----pter. Of the 48 single-copy fragments isolated from this new phage library, 39 (81%) were found to be chromosome 16 specific. Probes mapping to chromosome 16 were regionally localized by hybridizing to flow-sorted spot blots of translocation products from lymphoblastoid cell lines containing the rearrangements t(1;16) or t(11;16). Translocation breakpoints at 16p13.11 and 16p11.1 were utilized to subdivide chromosome 16 into three regions: Twenty-six probes were mapped to 16p11.1----16qter, two to 16p11.1----16p13.11, and eleven to 16p13.11----16pter. Probes from 16p were examined for their recognition of restriction fragment length polymorphisms (RFLPs). Seven polymorphic probes were found which recognized eleven RFLPs. Six of the seven probes have RFLPs which are reasonably informative (polymorphism information contents (PIC) of over 0.25). Two of these identify polymorphisms with three different alleles, one of which has a PIC value of over 0.4. These probes may aid in the diagnosis of APKD and contribute towards a linkage map of chromosome 16.

The genomic components identified by each of two closely related cDNA clones for the major 35 kilodalton non-serum surfactant-associated proteins (PSP-A) were shown to derive from human chromosome 10 by Southern blot analysis of DNAs from human-rodent somatic cell hybrids. By in situ hybridization to human metaphase chromosomes, the cDNA probes were localized to the region 10q21-q24.

The gamma-crystallins of the human eye lens are encoded by a multigene family of which at least six genes have recently been assigned to chromosome 2. We have now localized these genes to the distal region of the long arm of chromosome 2 (region q33-36, most probably q34-35) using somatic cell hybrids containing different parts of this chromosome and by in situ hybridization. The gamma-crystallin genes map to the same chromosomal region as IDH-1. Similar linkage exists between the loci Len-1 and Idh-1 on mouse chromosome 1.

The locus encoding the human T lymphocyte cell surface antigen Leu-2 has been assigned to chromosome 2 with a DNA mapping panel derived from somatic cell hybrids. The two genomic components identified by a cDNA clone for Leu-2 segregated with human chromosome 2 in all 24 independent hybrid clones examined. The cosegregation of the Leu-2 and immunoglobulin kappa (IgK) loci in hybrids with spontaneous rearrangements of chromosome 2 is consistent with the possibility that the Leu-2 locus is on proximal human 2p near IgK. In the mouse, a locus for a T lymphocyte cell surface antigen with properties similar to Leu-2 is closely linked to the IgK locus on mouse chromosome 6. Hence the syntenic relationship of a gene implicated in T cell killing with the immunoglobulin kappa locus would then be conserved in the mouse and human genomes.