Hemin treatment increased both activity and mRNA level of heme oxygenase in human macrophages. Using poly(A)‐rich RNA prepared from human macrophages treated with hemin, we have constructed a cDNA library in the Okayama‐Berg vector. The human heme oxygenase cDNA was isolated by screening this library with a rat cDNA and was subjected to nucleotide sequence analysis. The deduced human heme oxygenase is composed of 288 amino acids with a molecular mass of 32800 Da. The homology in amino acid sequences between rat and human heme oxygenase is 80%. Like rat heme oxygenase, human enzyme has a putative membrane segment at its carboxyl terminus, which is probably essential for the insertion of heme oxygenase into endoplasmic reticulum. Both rat and human heme oxygenase have no cysteine residues. Recently we have shown that rat heme oxygenase is a heat‐shock protein [J. Biol. Chem. 262, 12889–12892 (1987)], and therefore we examined the effects of heat treatment on the induction of heme oxygenase in human macrophages and glioma cells. In contrast to hemin treatment, heat treatment had no apparent effects in either human cell line on the activity of heme oxygenase and its mRNA levels. These results suggest that human heme oxygenase may not be a heat‐shock protein.

Steroid 11 beta-hydroxylase deficiency is relatively frequent in Israel among North African Jews. Over a 39-year period, 38 affected individuals from 25 families were diagnosed. Nineteen families came from Morocco, and in another 2, one parent came from Morocco (80% of all parents). Demographic studies showed that most of their grandparents were born in the region of the Atlas Mountains. In Israel, the overall incidence of the disorder is estimated between 1 in 30,000 to 1 in 40,000 births, but in offspring of Moroccan Jews the ratio is 1 in 5,000 to 1 in 7,000, with an allele frequency of 1 in 70 to 1 in 84 and a carrier frequency of 1 in 35 to 1 in 42. The clinical expression is characterized by a wide range of variability in the signs of androgen and mineralocorticoid excess. Virilization in the female ranged from enlarged clitoris in the mildest forms, to markedly hypertrophied clitoris with penile urethra and fused labial-scrotal folds in the most severe forms. Hypertension causing vascular accidents and death was observed in both severe and mildly virilized patients, whereas masculinized females were sometimes normotensive. Based on historical evidence, the origin of the ancestors, and the onomastic analysis of the families surnames, we propose that the mutation of 11 beta-hydroxylase deficiency in Jews from Morocco may have originated in either the ancient Jewish settlers or the native Berber tribes who lived in the region of the Atlas Mountains in the southern region of Morocco before the destruction of the Second Temple by the Romans, in the year 70 C.E.

A four-generation family was studied in which nine children had congenital cerebral palsy (CP), characterized by quadriplegia and mental retardation. All the affected children were born to healthy, related fathers, whereas the children of their healthy female relatives were unaffected. Linkage analysis attributed the condition to chromosome 9p24.3, where a 225 kb deletion was identified. The deletion spans a single gene, ANKRD15 (ankyrin repeat domain 15), which is ubiquitously expressed. In the affected children, the ANKRD15 is not expressed in lymphoblastoid cells, whereas in their healthy fathers, who harbor the same deletion, the expression of ANKRD15 did not deviate from controls. This expression pattern can be interpreted as a maternal imprinted gene that is expressed only from the paternal allele. The expression of ANKRD15 in lymphoblastoid cells from the control group was monoallelic but not imprinted. The monoallelic expression was restricted to the ANKRD15 gene, whereas biallelic expression was found in the DOCK8 gene, which resides at the telomeric side of the deletion. No correlation was found between the expression of the ANKRD15 gene and the pattern of DNA methylation in the CpG islands 5' of the gene. However, differences in methylation pattern were found in the CpG islands flanking the DMRT1 gene, which is located at the 3' side of the ANKRD15 gene. In the affected individuals, as in the control group, the CpG islands were hypo-methylated, whereas in the healthy fathers, the CpG islands were hyper-methylated in cis with the deletion. This unique family demonstrates a phenomenon of a deletion that creates imprinting-like inheritance. The implication of this family to sporadic CP is discussed.

The results showed high consanguinity rates in Muslim Arabs (42%), Christian Arabs (22%) and in Druze (47%). Rates of first cousin and closer matings in Muslim Arabs and Druze were stable over time in contrast with a significant decrease in the rates of distant consanguineous matings. Muslim Arab husbands (not Bedouins) who were sons of first cousins were more frequently (31%) married to a cousin than were other husbands (22%), and in Bedouins these rates were 53% and 33%, respectively. The rate of first cousin matings was predominantly associated with the level of education. The rate was highest in those Bedouins (37%) and Druze (37%) with low educational level, and lowest in highly educated Christian Arabs (14%) and non-Bedouin Muslim Arabs (10%). The association with education has implications for developing strategies for reducing consanguinity rates.

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