Hypogonadism, erectile dysfunction, and infertility in men
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Two Y-specific candidate gene families have been cloned by deletion mapping of infertile men with Yq deletions and proposed as candidates for the putative AZF locus, the RBM (RNA-binding motif containing) gene family247,253 and the DAZ (deleted in azoospermia) gene family.250,254–256 Both are multiple-copy gene families256,257 that contain the RNA-binding motif. The RBM gene family has more than 30 copies spread throughout the Y chromosome, most of the copies being located in deletion intervals 6A and 6B. At least two members of the RBM gene family, RBM-1 and RBM-2, are expressed in the testis.257 The presence of the RNA-binding motif in the predicted protein sequence suggests that these genes play a role in RNA processing; however, the precise role of the RBM proteins in germ cell development remains unclear.
Genetics of Endocrine Disorders and Diabetes Mellitus
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
MEN1 patients manifest tumors of the anterior pituitary, the parathyroid glands, and the pancreatic islets. Adrenocortical and thyroid tumors are occasionally associated with the syndrome.1 The disorder is inherited in an autosomal dominant manner. The MEN1 gene has been mapped to chromosome 11q13 by linkage analysis.2 Two recent papers propose two different genes in the area of the chromosome linked to the syndrome. The first proposes a gene termed ZFM1 (for zinc finger gene in the MEN1 locus). The nucleotide sequence of the clone predicts a gene containing 14 exons and 623 amino acids, part of which appears to be a metal-binding domain (zinc finger motif), which is seen in nucleic acid-binding proteins. The putative protein has some similarity to the Wilms’ tumor gene product and the early growth response 2 protein.3 The other proposed gene is nearby on chromosome 11q13 and was located using deletion mapping of parathyroid tumors. This gene codes for a previously described protein, phospholipase C β3 (PLC β3), which, based on the activity of similar proteins, may be involved in signal transduction, intracellular calcium regulation, or activation of protein kinase C, which are in turn involved in cell growth and differentiation.4 There are no studies to date showing specific defects in either of these genes that cosegregate with MEN1 syndrome in affected families, so it is not yet clear which, if either, of these genes is responsible for the syndrome.
Ribosomal RNA Processing Sites
S. K. Dutta in DNA Systematics, 2019
In prokaryotes, the RNA spacer sequences which immediately flank mature 16S rRNA within the pre-rRNA are able to form a long basepaired stem which loops out the entire 16S molecule.24 Such long stable stems cannot be formed in yeast,58Xenopus laevis,123a mouse,123b or maize.95 Only stems of much lower stability can be proposed, which are not supported by comparative analysis of these eukaryotic sequences. An absence of physical interaction between the 5′ end and 3′ cleavage sites (sites 1 and 2) is also consistent with the observation that the two cleavages are temporally separate events in higher eukaryotes: cleavage at site 1 largely precedes cleavage at site 2. More direct evidence that interactions between the regions surrounding the 5′ and 3′ ends of 18S rRNA is not required in specifying cleavage at site 1, has recently been reported by Bowman123c using cell transfection and deletion mapping techniques for analyzing the fate of transcripts from truncated mouse rRNA genes.
Learning about quantitative genetics from Marla Sokolowski
Published in Journal of Neurogenetics, 2021
Ralph J. Greenspan
Localizing genes for quantitative traits by conventional recombination mapping is always a formidable challenge because environmental variation, minor genes, and genetic markers have modifying effects on continuously varying phenotypes such as foraging. To compensate for this, de Belle and colleagues used ‘lethal tagging’ and deletion mapping to localize the gene to the left arm of chromosome 2. This involved generating radiation-induced lethal alleles that would fail to complement the recessive sitter phenotype. The result provided a salivary-chromosome-band level of resolution. The last necessary link came from seeing in the literature that the structural locus for one of the two cGMP-dependent protein kinases in Drosophila (dg2) mapped to the same salivary chromosome band (Kalderon & Rubin, 1989) as foraging.
Importin-α2 mediates brain development, learning and memory consolidation in Drosophila
Published in Journal of Neurogenetics, 2020
Christine N. Serway, Brian S. Dunkelberger, Denise Del Padre, Nicole W. C. Nolan, Stephanie Georges, Stephanie Freer, Andrew J. Andres, J. Steven de Belle
At the time we initiated this study, crude recombination data based on the mbmB brain histology phenotype indicated a position at 2–31 on the left arm of chromosome-2 (Heisenberg et al., 1985). Since mbmB females were observed to be sterile (de Belle & Heisenberg, 1996; Ginsburg, 2002) we leveraged this more expedient phenotype in further analyses (Figure S3(A)). A comprehensive deletion mapping experiment (>165 deletions/mbmB scored for female sterility) revealed that Df(2L)BSC50 (BSC50) failed to complement mbmB: all transheterozygous females were sterile with small MBs (Figure 2(A,B); see Supplementary Figure S3(B) for details). Overlapping deficiencies complimenting mbmB restricted our map designation to 30F4-6. Sequencing in this region identified a G-to-A transition in codon #262 of Pen, encoding Imp-α2 (hereafter referred to as imp-α2; Figure 2(A)). This nonsense mutation leading to a premature stop codon in place of wild-type tryptophan was expected to generate a truncated Imp-α2 protein. Of 25 tested P-elements in this region, we identified PBacPenc05212 (c05212) that failed to complement mbmB. We also found that imp-α2D14 (D14), an established null allele (Török et al., 1995) was female sterile, had strongly reduced MBs and similarly did not complement mbmB (Figure 2(B)).
A. Linn Murphree, MD: the Mississippi man who conquered retinoblastoma and changed the fate of patients and their families
Published in Ophthalmic Genetics, 2022
Jesse Berry, Elias I. Traboulsi, Francis Munier
With his first NIH grant, he demonstrated by deletion mapping that the RB1 gene was located on chromosome 13q14. Subsequently, he developed a clinical referral practice focused on pediatric ocular oncology and created the largest retinoblastoma referral center west of the Mississippi at CHLA—the Center continues to thrive. As a result of his clinical practice, Dr. Murphree recognized an unmet need for a wide-field retinal camera to document the intraocular findings associated with retinoblastoma. He recruited a team of optical engineers and collaborated with others in private industry to develop the RetCam®, a widely used and commercially available pediatric retinal camera that has facilitated the care of patients with retinoblastoma and other retinal diseases, including retinopathy of prematurity.
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