| 1. |
- Eklund, Julie A., et al.
(author)
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Assessing the effects of conservation treatments on short sequences of DNA in vitro
- 2010
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In: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 37:11, s. 2831-2841
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Journal article (peer-reviewed)abstract
- Little is known about what effects conservation treatments used to preserve human and animal hard and soft tissues have on DNA preservation. We have developed a method to assess quantitatively the extent of lesions or strand breakage caused by conservation treatments on short sequences of DNA in vitro. The method developed enables the determination of the percentage of DNA preserved following exposure to a conservation treatment solution relative to control samples, thereby allowing the direct comparison of treatments based upon their preserving/damaging effects on a DNA sequence. Forty-three chemicals commonly used in the preparation and/or conservation of human and/or animal remains were examined. We found that the majority were damaging, in particular and as expected, acidic treatments and treatments carried out at elevated temperatures. A few, primarily organic solvents, were not damaging. The approach we have adopted can be applied to screen other treatments either used in the past or for future conservation applications as they are developed to assess their effects on DNA. How these results should be interpreted in terms of conservation and sampling is also discussed.
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| 2. |
- Johnstone, Devon L., et al.
(author)
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Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature
- 2020
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In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:6, s. 1321-1332
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Journal article (peer-reviewed)abstract
- We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.
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