| Teaching |
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I currently teach various aspects of molecular genetics and human genetics
to undergraduate science, medical and dental students. An outline of my
courses and all courses taught by staff in the Department of Biochemistry
are available at UCC
Book of Modules.
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| Additional Links |
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| Research Interests
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| Human Genetic Disease/pharmacogenetics |
| Our major interest is in understanding the genetic basis of the muscle
disorders malignant hyperthermia (MH) and central core disease (CCD) in
humans. MH is a pharmacogenetic disorder of skeletal muscle where susceptible
individuals react adversely and sometimes fatally to common anaesthetic
agents. Pigs selected for high muscling (hypertrophy) also have this trait
and can suffer from stress-induced death. CCD individuals are also susceptible
to anaesthetic agents and often suffer from muscle atrophy (wasting) and
weakness. Our work in the Cork MH group http://www.ucc.ie/ucc/depts/biochemistry/jh/imh.html
has been aimed at identification of the genes and mutations responsible
for these disorders with a view to understanding their pathophysiology.
Work from our group and others has showed that the ryanodine receptor type
I (RYR1) in skeletal muscle cells is the main gene involved in MH and CCD.
Our current work is aimed at determining how abnormal release of calcium
through the RyR1 channel in muscle can lead to a) an adverse reaction to
anaesthetic agents in susceptible individuals, b) muscle weakness and muscle
wasting in CCD cases and c) muscle growth/hypertrophy in animals. |
| Related Publications |
Lynch PJ, Tong J, Lehane M, Mallet A, Giblin L, Heffron JJ, Vaughan P,
Zafra G, MacLennan DH, McCarthy TV.
A mutation in the transmembrane/luminal domain of the ryanodine receptor
is associated with abnormal Ca2+ release channel function and severe central
core disease.
Proc Natl Acad Sci U S A. 96:4164-9 (1999) |
Tong J, McCarthy TV, MacLennan DH.
Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size
in HEK-293 cells transfected with malignant hyperthermia or central core
disease mutant Ca2+ release channels.
J Biol Chem. 274:693-702 (1999) |
McCarthy TV, Quane KA, Lynch PJ.
Ryanodine receptor mutations in malignant hyperthermia and central core
disease.
Hum Mutat. 2000;15:410-7 (2000) |
Mackrill JJ, O'Driscoll S, Lai FA, McCarthy TV.
Analysis of Type 1 Ryanodine Receptor-12 kDa FK506-Binding Protein Interaction.
Biochem Biophys Res Commun. 285:52-7 (2001) |
Urwyler, A., Deufel, T., McCarthy, T., West, S. Br.
J. Anaesth.
Guidelines for molecular genetic detection of susceptibility to malignant
hyperthermia
86: 1-5 (2001) |
McCarthy TV, Datar S, Mackrill JJ.
Activation of ryanodine receptor/Ca2+ release channels downregulates CD38
in the Namalwa B lymphoma.
FEBS Lett. 554:133-7 (2003) |
McCarthy, TV. Malignant Hyperthermia. Nature Encyclopedia
of the Human Genome
(www.ehgonline.net/) |
| Genetic Technologies |
| Detection and tracking of variations (polymorphisms) in DNA is essential
for locating genes that cause susceptibility to genetic disease. Current
technologies in this area have significant limitations for this purpose.
Our work is aimed at developing improved methods for polymorphism detection
in DNA through exploitation of DNA repair enzymes. A continuing goal in
this area is to develop rapid and improved methods for high throughput genotyping
of single nucleotide polymorphisms (SNPs) in DNA. In our work to date, we
have developed a novel process for SNP detection. This process is referred
to as glycosylase mediated polymorphism detection (GMPD) and exploits the
use of highly specific DNA glycosylase enzymes to excise substrate bases
incorporated into amplified DNA. Our current aim is to further develop GMPD
as a tool for large scale genome analysis. |
| Related Publications |
Vaughan, P. and McCarthy, T.V.
(Forfas trading as BioResearch Ireland and UCC)
International patent application no. PCT/IE 95/00067
"glycosylase mediated
mutation detection of nucleotide sequences at candidate loci" (1995). |
Vaughan, P. and McCarthy, T.V.
A novel process for mutation detection using uracil DNA-glycosylase.
Nucleic Acids Research, 26, 810-815 (1998). |
McGrath, A.B., Vaughan., P.M. and McCarthy, T.V.
A DNA glocosylase-based fingerprint for accurate identification of amplified
DNA products and its application in the accurate diagnosis of infectious
organisms.
Anal. Biochemistry 259: 288-292 (1998). |
Vaughan P, McCarthy TV.
Glycosylase mediated polymorphism detection (GMPD)--a novel process for
genetic analysis.
Genet Anal. 14:169-75 (1999) |
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| Full Publication List |
|
www.ncbi.nlm.nih.gov/PubMed
search PubMed for McCarthy TV |
