Ideogram of chromosome 18 displaying positions of the functional genes along the linkage interval (Chr18p11.32-p11.31 on GRCH37/hg19 assembly) of 3.03 Mb identified in the family.

<p>Ideogram of chromosome 18 displaying positions of the functional genes along the linkage interval (Chr18p11.32-p11.31 on GRCH37/hg19 assembly) of 3.03 Mb identified in the family.</p

Two-point LOD score between ED syndrome and SNP markers on chromosome 18p11.32-p11.31.

<p><b>a</b> Physical positions of the SNPs are according to the dbSNP132 (<a href="http://genome.ucsc.edu/cgi-bin/hgGateway" target="_blank">http://genome.ucsc.edu/cgi-bin/hgGateway</a>)</p><p><b>b</b> Recombination fraction.</p><p>Two-point LOD score between ED syndrome and SNP markers on chromosome 18p11.32-p11.31.</p

<i>In Silico</i> Analysis of Missense Mutations in <i>LPAR6</i> Reveals Abnormal Phospholipid Signaling Pathway Leading to Hypotrichosis

<div><p>Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (<i>LPAR6</i>) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p.I188F in three other families. Molecular modeling and docking analysis was performed to investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T, L277P) LPAR6 receptors. The mutant receptors showed a complete shift in orientation of LPA at the binding site. In addition, hydropathy analysis revealed a significant change in the membrane spanning topology of LPAR6 helical segments. The present study further substantiated involvement of LPAR6-LPA signaling in the pathogenesis of hypotrichosis/woolly hair and provided additional insight into the molecular mechanism of hair development.</p></div

Missense mutations and the resultant phenotypes observed in the families described in the present study.

<p>Missense mutations and the resultant phenotypes observed in the families described in the present study.</p

Residual contributions explored through molecular dockings of LPAR6^WT and LPA binding.

<p>Labels are indicated by black color. Individual α-helices are indicated by distinct colors: α1, magenta; α2, green; α3, cornflower blue; α4, brown; α5, pink; α6, orange red and α7, olive. Loop regions and β-sheets are indicated by gold color.</p

Pedigree of a consanguineous Pakistani family segregating an autosomal recessive form of a novel type of ectodermal dysplasia.

<p>Circles and squares represent females and males, respectively. Clear symbols represent unaffected individuals while filled symbols represent affected individuals. Symbols with asterisk represent DNA samples available for the molecular analysis.</p

Comparative binding analysis of LPAR6^WT and LPAR6^MT structures bound to LPA. Similar residues in multiple complexes are indicated in bold.

<p>Comparative binding analysis of LPAR6^WT and LPAR6^MT structures bound to LPA. Similar residues in multiple complexes are indicated in bold.</p

Characterization of LPAR6 specific mutations at structure level.

<p>(A) 3D representation of LPAR6structure in ribbon form. Individual α-helices are indicated by distinct colors: α1, magenta; α2, green; α3, cornflower blue; α4, brown; α5, pink; α6, orange red and α7, olive. β-sheets are indicated by yellow color. (B) Schematic representation of LPAR6 secondary structures indicating the directionality of β-sheets to the extracellular part, while narrow end of α-helices points to the cytosol, making a groove-like structure. Corresponding positions of known amino acids undergoing substitutions are indicated which show that I188, N248 and L277 lie to the extracellular part of α-helices, while D63 and G146 residues are near the cytosolic part. Surface view of groove-like structure is shown to visualize the residual positions. (C) Hydropathy plot analysis of normal and mutated LPAR6 amino acids performed by MPEx tool. (D) Membrane spanning profile studies of individual α-helices for LPAR6^WT, LPAR6^D63V and LPAR6^N248Y.</p

Hydropathy analysis results for LPAR6^WT, LPAR6^D63V and LPAR6^N248Y proteins.

<p>Hydropathy analysis results for LPAR6^WT, LPAR6^D63V and LPAR6^N248Y proteins.</p

Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences-3

<p><b>Copyright information:</b></p><p>Taken from "Synpolydactyly and HOXD13 polyalanine repeat: addition of 2 alanine residues is without clinical consequences"</p><p>http://www.biomedcentral.com/1471-2350/8/78</p><p>BMC Medical Genetics 2007;8():78-78.</p><p>Published online 11 Dec 2007</p><p>PMCID:PMC2222244.</p><p></p>es. , (subject IX-23); , (IX-20); , (VIII-24); , (IV-7); , (III-3); , (V-6); , (V-3). Phenotypic categories are given in Figure 3