Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried the connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin.

The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%.

Certain germline mutations in either BRCA1 or BRCA2 confer a lifetime risk of developing breast cancer that may approach 90%. The BRCA1 185delAG mutation was found in 20% and the BRCA2 6174delT mutation in 8% of Ashkenazi Jewish women with early-onset breast cancer. The 185delAG mutation was observed in 0.9% of 858 Ashkenazi Jews unselected for a personal or family history of cancer. Assuming comparable age-specific penetrances, a carrier frequency of 0.3% was estimated for the 6174delT BRCA2 mutation. To test this hypothesis, we performed a population survey of 1,255 Jewish individuals. In two independent groups, a prevalence of approximately 1% (C.I. 0.6-1.5) was observed for the 6174delT mutation. The relative risk of developing breast cancer by age 42 was estimated to be 9.3 (C.I. 2.5-22.5) for 6174delT, compared to 31 (C.I. 11-77) for 185delAG. Analysis of 107 Ashkenazi Jewish women with breast cancer and a family history of breast or ovarian cancer confirmed a four-fold greater prevalence for the BRCA1 185delAG mutation compared to the BRCA2 6174delT mutation. Our findings suggest a difference in cumulative life-time penetrance for the two mutations. Genetic counseling for the one in 50 Ashkenazi Jewish individuals harbouring specific germline mutations in BRCA1 or BRCA2 must be tailored to reflect the different risks associated with the two mutations.

Hearing loss in Turner syndrome.

A retrospective study was undertaken to answer the following questions: Is the sensorineural hearing loss (SNHL) in Turner syndrome progressive? Can the occurrence of hearing loss be explained by the parental origin of the intact X chromosome? Twenty-four individuals recruited through the Turner Syndrome Society completed a questionnaire and submitted sufficient medical records to determine their otologic status. The majority (21/24) have had problematic otitis media (OM), and two thirds (16/24) have SNHL. In seven of the Turner subjects (age range: 12 to 51 years), gradual progressive SNHL began in late childhood or early adulthood. Molecular techniques showed no correlation between parental origin of the retained X chromosome and hearing status in 17 Turner subjects and at least one of their parents. SNHL and frequent OM appear to be independent variables that are both present in Turner syndrome. It is postulated that the presence of unpaired genes on the X chromosome may account for hearing loss and other phenotypic abnormalities seen in this syndrome.

Phase locking counterrotating modes of a broadband ring dye laser.

We present the results of an experimental study of phase locking counterrotating modes in a Rhodamine-6G continuous-wave broadband ring dye laser. Results for the measured mutual coherence of the counterrotating fields are presented for three different coupling geometries: namely, coupling by using an intracavity retroreflector, a single extracavity retroreflector placed in one of the output beams,and extracavity retroreflectors placed in each of the two output beams. We find that the highest degree of locking is obtained for the case of the intracavity retroreflector and leads to counterrotating outputswith a measured mutual coherence of unity.

Enhanced holographic image intensification in BaTiO(3) photoelectrets.

We report an enhanced holographic image amplification gain of over 24,000 at a wavelength of 514.5 nm by using a BaTiO(3) photoelectret. The energy-transfer efficiency and amplification factor are found to depend on critical polarization conditions of the photoelectret, the beam-mixing geometries, and the intensity ratios between the reference and the object beams. The results obtained corresponding values reported previously.

Experimental properties of an unstable resonator with nonuniform magnification using aspheric mirrors: errata.

This errata Letterpoints out two omissions in the original paper.

Effect of focal intensity on stimulated-Brillouin-scattering reflectivity and fidelity.

We have measured the reflectivity and phase-conjugate fidelity of stimulated Brillouin scattering in hexane while varying the pump power and aberration. By directly measuring the reduction in focal intensity that is due to aberrations, we found that the reflectivity and the fidelity depend solely on the focal intensity. We were able to vary the strength of aberration, producing up to a factor-of-30 reduction in focal intensity. The reflectivity and fidelity decreased monotonically with decreasing focal intensity. There was no minimum amount of aberration required for accurate wave-front reversal, and the maximum amount was the aberration that reduced intensity to near threshold.

Unstable ring resonator with a compact output beam: description and experimental evaluation.

A novel type of unstable resonator is described, and its operation with a CO(2) laser is discussed. The laser mode is rectangular in cross section, and the field is inverted about a line that makes a 45 degrees angle with the edge of the beam during a round-trip pass. Beam inversion, low magnification, and reasonably low sensitivity to misalignment allow efficient power extraction from low-gain lasing media while also outcoupling a solid rectangular beam. A beam quality of 1.1 was observed. The beam quality varied from 1.1 to 1.6 during misalignment of the rear rooftop mirror by ~0.06 mrad. A further misalignment of ~0.03 mrad stopped the lasing.

Variable phase grating optical aberrator.

We have developed and analyzed a heated laminar airflow device which introduces easily varied aberrations into optical beam trains. The aberrator produced nearly sinusoidal optical path differences of modulation depth 0 to 2lambda (peak to valley) at a 355-nm wavelength and a spatial frequency of ~2 cycles/cm. The phase modulation was measured via lateral shearing interferometry and agreed with a sinusoidal near field phase model to ~10%. The far field intensity profile was in qualitative agreement with the theory of focused sinusoidal phase gratings.

Experimental evaluation of an unstable ring resonator with 90 degrees beam rotation: HiQ experimental results.

The first experimental results on a confocal unstable resonator with 90 degrees beam rotation (UR90 or HiQ) are presented. A beam quality of 1.06 was observed, and it varied by a maximum of 0.08 over a resonator misalignment range of 1 mrad. The outcoupled beam's polarization was circular. Reverse mode suppression was achieved on UR90 with a suppressed vs unsuppressed ratio of 115:1. Measurable reverse mode suppression was obtained with as little as 2% of the full reverse mode strength. Most of these results are compared with those for a conventional ring resonator.

Experimental properties of an unstable resonator with nonuniform magnification using aspheric mirrors.

Laser resonators having nonuniform magnification can provide an advantage over constant magnification resonators in terms of energy extraction and far-field performance for low-gain lasers. This work explored the experimental characteristics of a resonator that was designed to have a lower magnification at the center of the resonator than at the edge. This was achieved using aspheric mirrors. Misalignment sensitivity, intracavity intensity, polarization, and collimation measurements were made. Results illustrate that some geometric properties were predictable and that aspheric mirrors can be used in resonator designs. In addition, the feasibility of using aspheric mirrors was evaluated. For certain applications, nonuniform magnification resonators using aspheric mirrors offer promising options.