Saethre-Chotzen syndrome is one of the most common autosomal dominant disorders of craniosynostosis in humans and is characterized by craniofacial and limb anomalies. The locus for Saethre-Chotzen syndrome maps to chromosome 7p21-p22. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype. We mapped TWIST to human chromosome 7p21-p22 and mutational analysis reveals nonsense, missense, insertion and deletion mutations in patients. These mutations occur within the basic DNA binding, helix I and loop domains, or result in premature termination of the protein. Studies in Drosophila indicate that twist may affect the transcription of fibroblast growth factor receptors (FGFRs), another gene family implicated in human craniosynostosis. The emerging cascade of molecular components involved in craniofacial and limb development now includes TWIST, which may function as an upstream regulator of FGFRs.

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Using somatic cell genetics and Southern blot hybridization, we have mapped five structural genes in the owl monkey, coding for catalase (CAT), the β-globin gene cluster (HBBC), c-Ha-ras 1 (HRAS1), insulin (INS), and parathyroid hormone (PTH). All five loci are mapped to chromosome 19 of karyotype VI (2n = 49,50) of the owl monkey; CAT, HBBC, INS, and PTH can be assigned to chromosome 4 of karyotype V (2n = 46), while CAT and HBBC can be assigned to chromosome 2 of karyotype III (2n = 53). Using in situ hybridization, the CAT gene was precisely mapped on the mid-region and the β-globin gene cluster on the telomeric end of chromosome 2q(K-ΠI). Our results provide significant insight into the evolutionary history of these gene loci. While these loci are separated into at least two major segments in rodents such as the mouse, our results suggest conservation of a single chromosome arm among higher primates.

We have mapped the albumin locus (ALB) in the owl monkey, Aotus trivirgatus, using a cloned human albumin gene probe, pcHSA 33-1. Rodent-owl monkey somatic cell hybrids were used to map the owl monkey albumin locus in three subgroups of Aotus, karyotypes II, V, and VI. Segregation analysis of the molecular hybridization pattern of pcHSA 33-1 in the somatic cell hybrids indicated that the albumin locus maps to chromosome 9 of owl monkey karyotype II, chromosome 12 of karyotype V, and chromosome 1 of karyotype VI. This assignment provides evidence for the homology of these three chromosomes and supports the hypothesis of Ma on the formation of chromosome 1 in karyotype VI.

Fluoresence in situ hybridization (FISH) was used to localize cosmids to regions of human chromosome 10. A total of 301 cosmids were selected randomly from a flow-sorted human chromosome 10 cosmid library constructed from human × hamster cell line 762–8A and arrayed in microtiter storage dishes. Over 70% (211/301) of the cosmids mapped to unique regions of chromosome 10. About 7% (22/301) produced multiple hybridization signals indicative of chimeric clones or sequences repeated at low copy number. Three cosmids (3/301, or 1 %) hybridized to the centromeric regions of chromosome 10 and one or more other human chromosomes. About 19% (59/301) consisted mostly or entirely of hamster DNA inserts, and about 2% (6/301) appeared to be nonrecombinants.