The genetics of isolated orofacial clefts: from genotypes to subphenotypes.

Orofacial clefts are the most common craniofacial birth defects and one of the most common congenital malformations in humans. They require complex multidisciplinary treatment and are associated with elevated infant mortality and significant lifelong morbidity. The development of craniofacial structures is an exquisitely orchestrated process involving the coordinated growth of multiple, independently derived primordia. Perturbations impacting on the genesis or growth of these primordia may interfere with the proper morphogenesis of facial structures, resulting in clefting of the lip, the primary or secondary palate, or a combination of these sites. A variety of genetic approaches involving both human populations and animal models have greatly facilitated the search for genes involved in human clefting. In this article, we review the most prominent genes for orofacial clefts in the context of developmental pathways that shape the craniofacial complex. We highlight several Mendelian clefting syndromes that have provided valuable clues in identifying genes for the more common, isolated forms of clefting. Finally, we elaborate on a number of potential subclinical features (subphenotypes) associated with what have previously been diagnosed as 'isolated' clefts that may serve as additional markers for identifying individuals or families in whom there may be a greater risk of inheriting a cleft.

Group velocity inversion in AlGaAs nanowires.

We investigated the dispersion characteristics of submicron sized AlGaAs waveguides. Numerical simulations shows that the tight confinement of the optical waves in such nanowires leads to strong variations of the dispersion characteristics compared to classic, weakly guided waveguides of the same material system. We found numerically that the investigated structure has negative GVD for the TE mode provided the waveguide width is between 670 nm and 280 nm. Experimental data obtained from 300 mum - 1 mm long wires confirms the numerical results.

Compact and integrated 2-D photonic crystal super-prism filter-device for wavelength demultiplexing applications.

A two-dimensional photonic crystal (PhC) super-prism integrated with one-dimensional photonic crystal microcavity filters has been designed using the plane wave expansion (PWE) and 2-D Finite Difference Time Domain (FDTD) methods based on Silicon-on-Insulator (SOI) technology. The super-prism operates as a coarse spatial filter with an average response bandwidth of 60 nm, while the 1-D PhC microcavity filters operate as narrow band-pass transmission filters with an average filter response line-width of 10 nm. This work demonstrates the simultaneous operation of two photonic devices for de-multiplexing applications on a single platform that could be useful in future Photonic Crystal Integrated Circuits (PCICs).

Platelet glycoprotein I(b)alpha and integrin alpha2 beta1 polymorphisms: gene frequencies and linkage disequilibrium in a population diversity panel.

Genetic variants in the GP1BA and ITGA2 genes have been proposed as potential modifiers for arterial vascular disease and bleeding disorders. Since ancestry may play an important role in the prevalence of these variants, we sought to determine their allele frequency and linkage disequilibrium in a collection of 1064 DNA samples from 51 ethnic groups. We studied haplotypes of ITGA2 defined by single nucleotide substitutions at positions -52, 807, and 1648, and GP1BA variants defined by sequence changes in positions -5 (Kozak), 1018 (T145M, HPA-2) and 1285 (VNTR A, B, C and D). Frequency of haplotypes of ITGA2 showed considerable variation across the different groups, with a higher prevalence of the haplotype -52C or T/807C/1648A observed in African compared with caucasian and Asian populations. The haplotypes 52C/807T/1648A and -52T/807T/1648A were not observed in caucasians or South Americans. While relative frequencies of the GP1BA Kozak alleles were comparable across groups, the methionine allele (HPA-2b) showed a higher frequency in Africa (0.26) than in the other groups. We also observed a high prevalence of the VNTR B allele in the African and Israeli populations. Haplotype analysis revealed incomplete linkage disequilibrium between the HPA-2 and VNTR alleles. Incorporation of GP1BA variants into the set of SNPs already genotyped by the HapMap project disrupted the pre-existing haplotype block. These data provide a valuable resource for optimal selection of variants best tailored for association studies of vascular disease or bleeding disorders when examining individuals of different ancestral origins.

Planar photonic crystal polarization splitter.

The differential dispersion relation for the E and H modes (TM-like and TE-like, respectively) in planar photonic crystals is used to control the polarization-dependent propagation of light. E- and H-polarized beams were separated by 10 degrees after propagating through a 20-microm-long planar photonic crystal in the wavelength range from 1250 to 1300 nm. The plane-wave expansion calculation matches well with the experimental results. This result represents the first demonstration, to our knowledge, of a polarization splitter realized in a planar photonic crystal configuration in the near-infrared wavelength range operating solely in transmission mode.

Engineering the filter response of photonic crystal microcavity filters.

Compact photonic crystal (PhC) filters will play a vital role in wavelength division multiplexing applications and they could be the stepping stones towards the realisation of dense and multifunctional photonic integrated circuits. Bragg grating concepts are applied to PhC filters to control their response by introducing suitable phase shifts and choosing appropriate locations and magnitudes. Moreover, the variation of the PhC hole size at the input and output regions could offer an extra degree of freedom in tailoring the filter characteristics. The ability to engineer and control the filter response of photonic crystal filters is investigated in this paper.

Enhanced detection of mutations in BRCA1 exon 11 using restriction endonuclease fingerprinting-single-strand conformation polymorphism.

A novel approach to mutation screening in the large exon 11 (comprising 3427 bp) of the human BRCA1 gene is presented. Restriction endonuclease fingerprinting single-strand conformation polymorphism (REF-SSCP) is based on repeated detection of DNA sequence variants in different restriction endonuclease fragments, and we evaluated the method using blood samples from 25 Norwegian patients with hereditary breast/ovarian cancer. We compared REF-SSCP to constant denaturant gel electrophoresis (CDGE) and to the protein truncation test (PTT). REF-SSCP detected 12 different DNA variants. Four of these were not detected by CDGE, and only one variant detected by CDGE was missed by REF-SSCP. PTT detected 4 of these 13 variants. REF-SSCP was subsequently applied to a second patient series (Swedish, n=20). A total of 14 different DNA variants were detected by REF-SSCP, 6 of which were truncating mutations (PTT detected only 4). Nonsense and frameshift mutations that are putative breast/ovarian cancer mutations, were detected in 7 of the 25 Norwegian and 9 of the 20 Swedish patients.