21 |
Methods for fine mapping complex traits in human pedigreesAbecasis, G. R. January 2001 (has links)
No description available.
|
22 |
FBI-1 amplification in gestational trophoblastic diseaseTam, Hoi-lam, Elizabeth, 譚凱琳 January 2014 (has links)
Gestational Trophoblastic Disease (GTD) encompasses a spectrum of disease that involves abnormal trophoblastic proliferation. It includes hydatidiform mole (HM), placental site trophoblastic tumor (PSTT), epithelioid trophoblastic tumor (ETT) and choriocarcinoma (CCA). While HMs are abnormal pregnancies with limited invasive potential, CCAs are true malignancies requiring chemotherapy. Although the majority of HM is resolved by surgical intervention, approximately 8-30% of them would develop into persistent GTD. In addition to that, being the most aggressive neoplasm in GTD, choriocarcinoma is a frankly malignant gestational trophoblastic neoplasm (GTN) that could be arisen from HM and could be fetal when widespread metastasis is developed. However, the underlying mechanisms of this disease progression are still unclear.
FBI-1 (Factor that Binds to Inducer of Short Transcripts (IST) protein 1) is a transcription factor that has been observed to be overexpressed in various types of human cancers. Recently, overexpression of FBI-1 is also reported in GTD and also in association with GTN development. However, the causes of FBI-1 overexpression in GTD are still unclear. This study aims to investigate gene amplification as a possible cause of FBI-1 overexpression in GTD. A quantitative real time PCR (qPCR) assay was established and was used to investigate ZBTB7A (the gene encoding FBI-1) amplification in GTD cell lines and clinical samples.
Using our qPCR assay, we demonstrated that ZBTB7A is not amplified in the CCA cell lines JEG-3 and JAR, in comparison with an immortalized trophoblast cell line HTR-8/SVneo. Testing ZBTB7A amplification in clinical samples also obtained similar findings although overexpression of FBI-1 was demonstrated in our previous studies. This is the first report illustrating absence of ZBTB7A amplification in cells with FBI-1 overexpression. There are other techniques that can detect gene amplification and/or other genetic and epigenetic mechanisms that may govern FBI-1 expression in GTD. Further studies will be worthwhile to pursue as FBI-1 is a potential target for cancer therapy. / published_or_final_version / Pathology / Master / Master of Medical Sciences
|
23 |
A study of the Bloom's syndrome proteinKarow, Julia K. January 1999 (has links)
Bloom's syndrome is a rare autosomal recessive disorder characterised by an early onset of cancer of many types, erythematous lesions on sun-exposed skin, retarded growth, immunodeficiency and sub- or infertility. Cells from Bloom's syndrome patients have replication defects and an abnormally unstable genome manifested in chromosomal breaks and deletions and in an increased mutation rate. Most characteristically, these cells show elevated levels of sister-chromatid exchanges which probably result from homologous recombination events. Since the cells are not hypersensitive to DNA damaging agents, the defect is unlikely to be in one of the common DNA repair pathways. The gene mutated in Bloom's syndrome, BLM, was cloned in 1995 and found to encode a helicase from the RecQ family. This family is named after its E. coli member, RecQ, and includes at least five human genes. Three of these are mutated in inherited disorders; Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome. In my DPhil project, I have investigated the enzymatic properties of the BLM protein. I have purified the protein in recombinant form and shown that it is a DNA-dependent ATPase and an ATP-dependent helicase with 3'-5' polarity. It binds and unwinds a variety of DNA structures, with a preference for tetraplex (G4)-DNA, Holliday junctions (recombination intermediates) and internal DNA bubbles. Furthermore, it is capable of branch migration, an activity distinct from its helicase activity. BLM forms oligomeric rings with fourfold and sixfold symmetry, both in a cell extract and as purified protein. These results, in combination with the cellular phenotype of Bloom's syndrome and with evidence from the analysis of other RecQ homologues in model organisms such as yeast and E. coli, point to a role for BLM in somatic recombination (recombinational repair). Models for this function are discussed in this thesis.
|
24 |
The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency /Worgan, Lisa Catherine. January 2005 (has links)
Thesis (M. Sc.)--University of New South Wales, 2005. / Also available online.
|
25 |
Comparison of three clustering methods for dissecting trait heterogeneity in simulated genotypic dataThornton-Wells, Tricia A. January 2005 (has links)
Thesis (M.S. in Biomedical Informatics)--Vanderbilt University, Aug. 2005. / Title from title screen. Includes bibliographical references.
|
26 |
Molecular analysis of GJB2 (connexin 26) and GJB6 (connexin 30) gene mutations in non-syndromic hereditary deafness in South AfricaWhitehead, Caragh (Caragh Bryony) 03 1900 (has links)
Thesis (MSc)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: The most common inherited sensory disorder that affects I in 1 000 children is severe hearing loss.
In developed countries, about a third of cases have a genetic origin, 80% of which are autosomal
recessive forms (DFNB). Before 1993 few genes causing hearing loss had been identified, but since
then a large number of genes related to this problem have been identified. Studies indicate that the
DFNBI locus, located at position 13q11-12, contributes to 20% of all childhood deafness and may
have a carrier rate as high as 2.8%. There are two genes linked to DFNB 1, GJB2 and GJB6, which
are the major genetic cause of non-syndromic autosomal recessive deafness. GJB2 and GJB6
encode the connexin proteins connexin 26 and 30 (Cx26 and Cx30), respectively.
The specific aim of this study was to determine the role of GJB2 and GJB6 in deafness within the
South African population, since there are no published results involving South African patients with
non-syndromic autosomal recessive deafness. This study therefore involved the identification of
mutations within the coding region of the GJB2 and GJB6 genes in the South African population
and the determination of their specific allele frequencies. Another aim of this study was to analyse
the effectiveness of three single-strand conformation polymorphic (SSCP) gel electrophoresis
systems in the detection of GJB2 mutations, for use in a standardised diagnostic program.
A total of 44 families were recruited and divided into either the familial or sporadic study group,
which consisted of 16 and 28 families, respectively. Control samples were also screened from 50
Caucasians and 50 Mixed Ancestry individuals collected from the general population. To achieve
the aims of this study, polymerase chain reaction (PCR) amplification followed by automated DNA
sequencing of the coding regions of GJB2 and GJB6 was performed. The three SSCP systems that
were tested for their effectiveness in detecting mutations within the coding region of GJB2 included
mini polyacrylamide, SSCP-urea and two buffer gel electrophoresis systems.
In total, six previously reported mutations (35delG, 312de1l4, W24X, M34T, V37I and W44X), a
novel mutation (N62I), and four benign polymorphisms (V27I, A40A, R127H and V153I) were
detected in GJB2. In the GJB6 gene only the S199T polymorphism was observed. It was
determined that the most common mutations found within the Caucasian and Mixed Ancestry
populations of South Africa were 35delG and 312de1l4 of GJB2. An overall detection rate of
35.227% was achieved in non-syndromic autosomal recessive deafness amongst this patient cohort.
It was also observed that none of the SSCP gel electrophoresis systems were effective at detecting all of the GJB2 mutations. This could change if the systems were specifically optimised for the
cornmon mutations that were identified.
This study therefore, provides information that can be used in the formulation of a screenmg
program for non-syndromic autosomal recessive deafness specific to the South African population.
Further research should be conducted involving other genes, in addition other population groups of
South Africa to provide a more comprehensive genetic diagnostic and counselling tool. / AFRIKAANSE OPSOMMING: Die mees algemene oorerflike sensoriese steuring wat 1 in 1 000 kinders affekteer is ernstige
gehoorverlies. In ontwikkelde lande het omtrent een-derde van die gevalle 'n genetiese oorsprong,
waarvan 80% outosomaal resessiewe vorms is (DFNB). Tot en met 1993 is min gene wat
gehoorverlies veroorsaak geïdentifiseer, maar sedertdien is 'n groot aantal gene gelokaliseer en
verskeie is ook al gekloneer. Studies toon dat die DFNB 1 loci, wat in posisie 13q 11-12 gevind
word, 20% van doofheid in kinders veroorsaak, en dit het 'n draer frekwensie van so hoog as 2.8%.
Twee gene wat koppeling met DFNBI toon, GJB2 en GJB6, is die vernaamste genetiese oorsaak
van nie-sindromise autosomaal resessiewe doofheid. GJB2 en GJB6 koder vir die connexin proteïne
26 en 30 (Cx26 en Cx30), onderskeidelik.
Die spesifieke doel van hierdie studie is om die rol van GJR2 en GJB6 in doofheid binne die Suid-
Afrikaanse populasie te bepaal, aangesien daar tans nog geen gepubliseerde resultate omtrent Suid-
Afrikaanse pasiënte met nie-sindromiese outosomaal resessiewe doofheid is nie. Hierdie studie
handel dus oor die identifikasie van mutasies wat binne die koderende areas van die GJR2 en GJB6
gene voorkom in die Suid-Afrikaanse populasie, asook oor die bepaling van hulle spesifieke alleel
frekwensies. Verder het hierdie studie ten doelom die effektiwiteit van drie enkel-string
konformasie polimorfisme (SSCP) gel-elektroforese metodes in die opsporing van GJB2 mutasies
te analiseer met die oog op toekomstige gebruik in 'n gestandardiseerde diagnostiese program.
Altesaam 44 families is ingesamel en gekategoriseer in familiële of sporadiese studie-groepe met 16
en 28 families onderskeidelik. Kontrole monsters van 50 Kaukasiese en 50 Gemengde Herkoms
individule uit die algemene populasie is ook getoets. Om die doeleindes van die studie te bereik is
PKR amplifikasie en outomatiese DNS volgordebepaling van die koderende area van GJB2 en
GJR6 gedoen. Die drie SSCP sisteme wat getoets is vir hulle effektiwiteit in die identifisering van
mutasies in die koderende area van GJB2 sluit in mini poli-akrielamied, urea en twee-buffer gel
elektroforese sisteme.
In totaal is ses gerapporteerde mutasies (35delG, 312de114, W24X, M34T, V37I en W44X), 'n
nuwe mutasie (N62I), en vier onskadelike polimorfismes (V27I, A40A, R127H en V153I)
opgespoor in GJB2, maar in GJB6 is net die S199T polimorfisme waargeneem. Uit die resultate kon
afgelei word dat 35deiG en 312de114 van GJB2 die mees algemene mutasies binne die Kaukasiese
en Gemengde Herkoms bevolkings van Suid Afrika is. Die total ontdekking standaard van 35.227%· vir nie-sindromise autosomaal resessiewe doofheid tussen herdie patient kohort was bereik. Verder
is waargeneem dat geen van die SSCP gel elektroforese metodes effektief was om al die mutasies
van GJB2 op te spoor nie. Die situasie kan egter verander as die sisteme spesifiek geoptimiseer
word vir die algemene mutasies wat gevind is.
Hierdie studie verskaf dus inligting wat gebruik kan word in die verskaffing van 'n diagnostise
program vir nie-sindromise outosomaal resessiewe doofheid wat spesifiek is vir die Suid-
Afrikaanse populasie. Verdere navorsing wat ander gene en ander populasie groepe van Suid-Afrika
insluit, behoort egter uitgevoer te word om uiteindelik 'n meer uitgebreide genetiese diagnostiese en
raadgewing diens daar te stel.
|
27 |
Zebrafish as a model of genetic disease.Tucker, Ben January 2008 (has links)
The zebrafish is rapidly becoming a vital tool in studies of genetic disease. Use of the zebrafish embryo as an experimental model combines the efficiency of techniques specific to invertebrates with the human applicability of vertebrate studies, along with a number of other advantages such as optical transparency and high spawn number. Sequencing maps and mutant screen data are available, and gene ontology annotation is progressing. Furthermore, a number of highly important projects are underway to expand the utility of the zebrafish still further (eg. Mutant screens and TILLING projects; see (Lieschke and Currie, 2007) for review). As such the zebrafish has become a vital model organism for study of a variety of genetic defects, toxicology and pharmacological screens etc. These papers trace the development of zebrafish embryos as a model organism for both genetic disease and, as part of this, the development of a relatively high throughput approach to analysing relative levels of apoptosis. The first paper describes the fmr1 gene family in zebrafish (fmr1, and its orthologs fxr1 and fxr2). This paper includes a phylogenetic analysis of the gene family that demonstrates the high conservation between human and zebrafish, in the context of Drosophila. We then describe expression of the genes in the embryo (using in situ hybridisation) and adult (using real time pcr). The conclusions are that the zebrafish is an appropriate model in which to study Fragile X Mental Retardation genetic disease. The second paper builds upon this conclusion and further establishes the appropriateness of the model by recapitulating elements of the disease that had already been modelled in other model organisms. The research is validated using a number of controls. We describe a number of original findings that extended the body of knowledge regarding pharmacological rescue of the FMRP loss phenotypes. A craniofacial phenotype is identified, the first such discovery in a model of Fragile X syndrome. These findings are a vital step toward understanding the pathway from gene, to molecular phenotype, to cellular morphology, to gross morphology. As part of these studies, we found it necessary to analyse apoptosis. The technique developed to facilitate this analysis is described in our third paper. Given the highly stochastic nature of the apoptotic patterns we developed a method to take full advantage of the characteristics of zebrafish embryos, primarily their transparency and availability in large numbers. As the zebrafish becomes more widely accepted as a model for a diverse range of scientific questions, the development of such a technique is doubly important given the necessity of a cheap, reliable and simple generalizable method of analysing processes affecting cell viability in fish. This has clear importance for pharmacological studies, but is also a long overdue addition to the battery of controls available for highly invasive techniques such as microinjection, in which apoptosis is regularly found among its non specific effects. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311173 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008
|
28 |
Psychological and behavioral outcomes of genetic testing for BRCA1/2 mutations among Ashkenazi Jewish Women /Ozakinci, Gozde. January 2004 (has links)
Thesis (Ph. D.)--Rutgers University, 2004. / Includes bibliographical references. Also available on the Internet.
|
29 |
Modelling human genetic disorders in miceMigdalska, Anna Marta January 2012 (has links)
No description available.
|
30 |
Investigations of ephrin ligands during development /Tosch, Paul. January 2002 (has links) (PDF)
Thesis (Ph.D.) -- University of Adelaide, Dept. of Molecular Biosciences, 2003. / "May 2002." Addendum inside back cover. Bibliography: p. 139-157.
|
Page generated in 0.0636 seconds