Papers by Robert Williamson
American Journal of Medical Genetics Part A, 2008
Human molecular …, 2004
Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents represents a poten... more Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents represents a potential strategy for the therapy of b-thalassemia, sickle cell disease, HbE and other b-hemoglobinopathies. However, the drugs currently available have low efficacy and specificity and are associated with high toxicity. We describe the development of stable cellular genomic reporter assays (GRAs) based on the green fluorescence protein (EGFP) gene under the G c-globin promoter in the intact human b-globin locus. We show that human erythroleukemic cell lines stably transfected with a G c-EGFP b-globin locus construct can maintain a uniform basal level of EGFP expression over long periods of continuous culture and that induction of EGFP expression parallels the induction of the endogenous globin genes. We compared the EGFP-induction potency of a number of chemotherapeutic agents, including histone deacetylase inhibitors and DNA-binding agents. We show that hydroxyurea and butyrate result in moderate levels of induction (70-80%) but with an additive inductive effect. Among the DNA-binding agents tested, cisplatin was the most potent inducer of HbF expression, (442 AE 32%), a level which is comparable to hemin (764 AE 145%). These results indicate that cellular GRAs containing G c-EGFP-modified b-globin locus constructs can be used to develop novel inducers of HbF synthesis for the therapy of b-hemoglobinopathies.
American Journal of Medical Genetics, 2007
Guidelines recommend that predictive genetic testing for
Huntington disease (HD) should be defer... more Guidelines recommend that predictive genetic testing for
Huntington disease (HD) should be deferred until the age of
majority (18 years in most countries). However, opposition
to these guidelines exists, with some professionals arguing
that testing may be beneficial for young people, and should
be considered much earlier. Empirical evidence is unable to
substantiate either position. We aimed to (1) explore the
experience of predictive genetic testing for HD from the
young person’s perspective and to (2) document the impact
that testing has upon various aspects of young people’s lives.
Eight young people who had undergone predictive genetic
testing for HD were interviewed. They ranged in age from 17
to 25 years at the time of their test. Four were female and two
had received a gene-positive test result. Interviews were
taped, transcribed and analyzed thematically. Three themes
emerged related to the time before the test was performed:
‘‘Living as though gene-positive,’’ ‘‘Risk behaviors,’’ and
‘‘Complex pasts.’’ Two themes emerged related to the time
after testing: ‘‘Identity difficulties’’ and ‘‘Living again.’’ When
the young people spoke about their experiences of predictive
testing, they placed these within a broader context of
growing up in a family affected by HD. For some of the
young people, uncertainty about their genetic status
constituted a barrier in their lives and prevented them from
moving forward. Testing alleviated these barriers in some
cases and helped them to move forward and make signi-
ficant behavioral changes. Not one of the young people
interviewed regretted undergoing predictive testing.
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Papers by Robert Williamson
Huntington disease (HD) should be deferred until the age of
majority (18 years in most countries). However, opposition
to these guidelines exists, with some professionals arguing
that testing may be beneficial for young people, and should
be considered much earlier. Empirical evidence is unable to
substantiate either position. We aimed to (1) explore the
experience of predictive genetic testing for HD from the
young person’s perspective and to (2) document the impact
that testing has upon various aspects of young people’s lives.
Eight young people who had undergone predictive genetic
testing for HD were interviewed. They ranged in age from 17
to 25 years at the time of their test. Four were female and two
had received a gene-positive test result. Interviews were
taped, transcribed and analyzed thematically. Three themes
emerged related to the time before the test was performed:
‘‘Living as though gene-positive,’’ ‘‘Risk behaviors,’’ and
‘‘Complex pasts.’’ Two themes emerged related to the time
after testing: ‘‘Identity difficulties’’ and ‘‘Living again.’’ When
the young people spoke about their experiences of predictive
testing, they placed these within a broader context of
growing up in a family affected by HD. For some of the
young people, uncertainty about their genetic status
constituted a barrier in their lives and prevented them from
moving forward. Testing alleviated these barriers in some
cases and helped them to move forward and make signi-
ficant behavioral changes. Not one of the young people
interviewed regretted undergoing predictive testing.
Huntington disease (HD) should be deferred until the age of
majority (18 years in most countries). However, opposition
to these guidelines exists, with some professionals arguing
that testing may be beneficial for young people, and should
be considered much earlier. Empirical evidence is unable to
substantiate either position. We aimed to (1) explore the
experience of predictive genetic testing for HD from the
young person’s perspective and to (2) document the impact
that testing has upon various aspects of young people’s lives.
Eight young people who had undergone predictive genetic
testing for HD were interviewed. They ranged in age from 17
to 25 years at the time of their test. Four were female and two
had received a gene-positive test result. Interviews were
taped, transcribed and analyzed thematically. Three themes
emerged related to the time before the test was performed:
‘‘Living as though gene-positive,’’ ‘‘Risk behaviors,’’ and
‘‘Complex pasts.’’ Two themes emerged related to the time
after testing: ‘‘Identity difficulties’’ and ‘‘Living again.’’ When
the young people spoke about their experiences of predictive
testing, they placed these within a broader context of
growing up in a family affected by HD. For some of the
young people, uncertainty about their genetic status
constituted a barrier in their lives and prevented them from
moving forward. Testing alleviated these barriers in some
cases and helped them to move forward and make signi-
ficant behavioral changes. Not one of the young people
interviewed regretted undergoing predictive testing.