Thesis (Ph. D.)--Swedish University of Agricultural Sciences, 2001. / Includes bibliographical references.

No description available.

Genomic clones were isolated and characterized using the human monoamine oxidase A (MAOA) cDNA to screen a phage library, constructed from a human 4X cell line (48, XXXX). The genomic contig derived from overlapping phage clones showed that the size of the MAOA gene is over 80 kb. Exon-containing fragments from these phage clones were subcloned and sequenced. The data from this showed that the MAOA gene consists of 15 exons. A YAC (yeast artificial chromosome) isolated using the MAOA cDNA was characterized. This YAC was found to contain both the MAOA and the MAOB genes. Using PFGE (pulsed-field gel electrophoresis) to investigate the YAC, it was found that the MAOA and the MAOB genes are located within 50 kb and adjacent to each other. The two genes are localized in a 3'-to-3' fashion, suggesting their expression may be regulated independently. The analysis of the homology shown by the two genes clearly demonstrated that they were derived from duplication of a common ancestral gene. A CpG island was discovered to be associated with the 5' end of both genes. A restriction map of -2.5 Mb of genomic DMA around the MAO genes was generated by PFGE. Long-range mapping defined the physical relationship between the marker L1.28 and the MAO genes as L1.28_MAOA_MAOB. A number of genetic diseases have been linked to the Xp11.3 region. Strong linkage was known to exist between the Norrie disease locus and L1.28. Studies showed that some of the Norrie patients have deletions encompassing the region which contains L1.28 as well as the MAO genes. Another YAC isolated by using L1.28 as the probe was also characterized. A phage library was constructed from the L1.28 YAC and the end clones were isolated. Studies on some of the Norrie deletion patients showed that the proximal end clone of the YAC was retained in one of the deletion patients. Previous studies had shown that the Norrie disease locus was also localized proximal to the 5' end of the MAOB gene. The combined information placed the disease locus to an interval of 240 kb within the YAC. More phage clones were characterized in order to define further the region for the Norrie locus which was finally localized within 160 kb. A YAC fragment of 160 kb was isolated and used to screen two human retinal cDNA libraries. Among the cDNAs isolated, one group was found to be deleted in some of the Norrie patients previously without any known deletion, which established their candidacy as the transcripts of the Norrie disease locus. Further characterization of the candidate gene showed that it is conserved across species. The expression of the gene was detected in various tissues. The homology shared between the NDP gene and some of the growth factor binding proteins suggests its role in neural cell proliferation and differentiation.

The hypervariable locus DXS255 in human Xp11.22 has a heterozygosity exceeding 90% and has therefore facilitated the localization of several disease genes which map to the proximal short arm of the X chromosome, including the immune deficiency Wiskott-Aldrich syndrome and the eye disorders retinitis pigmentosa, congenital stationary night blindness and Aland Island eye disease. In addition, a microdeletion involving DXS255 has been identified in patients suffering from Dent's disease, a familial X-linked renal tubular disorder which is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis (kidney stones) and eventual renal failure. Two YAC contigs were constructed in Xp11.23-p11.22 in order to aid transcript mapping; the first centred on the DXS255 locus, the second mapping distal to the first and linking the genes GATA, TFE3 and SYP to the OATL1 cluster. Eleven novel markers were generated, one of which contains an exon from a novel calcium channel gene. Four putative CpG islands were detected in the region. Analysis of the microdeletion associated with Dent's disease using markers from the DXS255 contig demonstrated that it is confined to a 370kb interval. A YAC overlapping this deletion was hybridized to a kidney-specific cDNA library to isolate coding sequences that might be implicated in the disease aetiology. The clones thus identified detect a 9.5kb transcript which is expressed predominantly in kidney, and originate from a novel gene (CLCN5) falling within the deleted region. Sequence analysis indicates that the 746 residue protein encoded by this gene is a new member of the C1C family of voltage-gated chloride channels. The coding region of CLCN5 is organized into twelve exons, spanning 25-30kb of genomic DNA. Using the information presented in this thesis, other studies have identified deletions and point mutations which disrupt CLCN5 activity in further patients affected with X-linked hypercalciuric nephrolithiasis, confirming the role of this locus in renal tubular dysfunction.

Thesis (Ph. D. in Cellular and Molecular Pathology)--Vanderbilt University, May 2009. / Title from title screen. Includes bibliographical references.

Thesis (MCIS - Computer and Information Sciences) --AUT University, 2007. / Includes bibliographical references. Also held in print (ix, 74 leaves : ill. ; 30 cm.) in City Campus Theses Collection (T 006.33 WAN)

Thesis (Ph.D.) -- McMaster University, 2002. / Includes bibliographical references (leaves 189-243). Also available via World Wide Web.

Genetic disorders like Cystic Fibrosis (CF) and X-linked Diseases (XLD) are inherited by offspring from parents who are healthy carriers of the autosomal recessive or allosomal genes. About 10-million Americans are healthy carriers of a mutant cysticfibrosis gene (predominantly F508del) and about 4% of newborns are at risk of being born with an X-linked disease. The current clinically approved mitigation plan for preventing genetic disorders in newborns from “at-risk couples” is to consider Preimplantation Genetic Testing for Monogenetic diseases (PGT-M). PGT-M involves an invasive microsurgical procedure that requires the removal of cells from 3-5day old embryos. To minimize this invasiveness, we proposed a less invasive approach to prevent genetic disorders in newborns by genotypically sorting sperm cells which may be used for fertilization events (IUI/IVF/ICSI) with specially characterized antigens on the sperm surface membrane. For the disease models being adopted in our study – CF and XLD; we utilized certain monoclonal antibodies (mab) to target the H-Y male antigen and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein which are both selectively expressed on the sperm surface. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

Indiana University-Purdue University Indianapolis (IUPUI) / Fanconi anemia (FA) is a genetic disorder characterized by bone marrow (BM) failure. Previous studies suggest that FA patients exhibit alterations in immunologic function. However, it is unclear whether the immune defects are immune cell autonomous or secondary to leucopenia from evolving BM failure. The aim of the current study was to determine whether FA type C deficient (Fancc-/-) macrophages exhibit impaired function and contribute to an altered inflammatory response. In this study, primary peritoneal macrophage function and the inflammatory response of Fancc-/- immune cells after in vivo intraperitoneal (IP) administration of lipopolysaccharide (LPS) were assessed. Fancc-/- peritoneum exhibit normal macrophage distribution at baseline. However, Fancc-/- macrophages exhibit reduced adhesion both on fibronectin and endothelial cells, impaired migration toward monocyte chemotactic protein-1 (MCP-1) and macrophages-colony stimulating factor (M-CSF), and altered phagocytosis of E.coli and ImmunoglobulinG (IgG)-labeled latex beads compared to WT. An altered F-actin reorganization and impaired activation of RhoA were observed in Fancc-/- macrophages. After single LPS injection IP, Fancc-/- mice exhibited decreased macrophage recruitment, reduced peripheral inflammatory monocytes and impaired myeloid colony formation in presence of M-CSF. Upon M-CSF stimulation, Fancc-/- BM derived macrophages (BMDM) showed a decreased phosphorylation of AKT and ERK compared to WT, leading to reduced proliferation. Collectively, these data suggest that Fancc-/- macrophages and subsequent defects in adhesion, migration, phagocytosis, and recruitment in vivo. These data also support a Fancc-/- macrophage cells autonomous defect predisposing to an altered inflammatory response.

Background: Autism spectrum disorder (ASD) is a lifelong developmental disability defined by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Over the last few decades, the global prevalence of autism has increased by twentyfold to thirtyfold. In the United States, the prevalence of ASD has increased rapidly with one out of every fifty-nine children (1.7%) diagnosed with the condition. With the increasing prevalence of ASD, the financial cost has been estimated to exceed those of Diabetes and Attention Deficit Hyperactivity Disorder (ADHD) by 2025. Furthermore, ASD has been found to be about 4-5 times more prevalent in males, compared to females, and there has been a noted increase in the prevalence of congenital abnormalities in patients with ASD. Objective: As part of an ongoing multi-year retrospective chart review of the patients seen at the Genetics Clinic for suspected or confirmed cases of ASD, we sought to identify the demographic characteristics of these patients and to see how they compare with documented studies. Methods: The overall study is an ongoing multi-year, retrospective chart review of patients seen at the ETSU Medical Genetics Clinic, with features suggestive of ASD. For this preliminary study, we extracted data from the Electronic health record (Allscripts) for 80 patients (n=80), on the gender, term status at birth (term defined as gestational age at delivery of 37 weeks or more, preterm defined as those delivered at less than 37 weeks), twin status, presence of congenital abnormalities, and the state of residence. We entered all the extracted data into REDCap and carried out a descriptive analysis of the data using the Statistical Package for Social Sciences (SPSS). Results: It was found that of the eighty patients, eighteen (22.5%) were females while sixty-two (77.5%) were males, (male to female ratio of 3.4 to 1). Fifty-nine patients (73.8%) were born at term, eighteen (22.5%) born preterm and three (3.8%) with unknown term status. Seventy-seven patients (96.3%) were twins and three (3.8%) were not. Thirty patients (37.5%) had no congenital abnormalities at birth while fifty patients (62.5%) had at least one congenital abnormality at birth. Sixty-one patients (76.3%) were from Tennessee while nineteen (23.8%) were from Virginia. Conclusions: This preliminary finding revealed an increased proportion of males compared to females, as well as an increased proportion of the population with congenital abnormalities compared to those without such abnormality. These findings agree with documented data from previous studies on ASD. In our future analysis, we would examine the rate of diagnosis of ASD in the clinic, the type of mutation and the genes involved and identify any trend for specific genes, and/or specific mutation.