We have identified a family in which three females carry both the male and female variants of the amelogenin gene. The father of the female proband types male, as expected. The mother of the proband is deceased and cannot be tested. The sister as well as the daughter of the proband also have the amelogenin male variant. We have been unable to determine when this male variant became associated with a female X chromosome, although identification of these three females with the male variant shows its Mendelian inheritance within this family. The proband was investigated for 16 genetic markers, other than amelogenin, that are known to be Y chromosome specific. She did not have any of this male-specific DNA. The male-specific amelogenin variant from the proband was cloned and sequenced, which showed it to be identical to the published male Y chromosome sequence of the amelogenin gene. The data are novel and have implications for those performing sex determination assays using the amelogenin locus, as well as for geneticists interested in the extent of gene conversion events involving the X and Y chromosome.

Hemihypertrophy, or hemihyperplasia, is a condition in which there may be asymmetrical overgrowth of the cranium, face, trunk, and/or limbs on one side of the body.1 There may also be asymmetrical visceromegaly on the ipsilateral or contralateral side.2 Hemihypertrophy may occur in isolation, hence the term “isolated hemihypertrophy (IH)”, or as part of a number of overgrowth syndromes in which other characteristic clinical features are present. Such syndromes include neurofibromatosis, Klippel-Trenaunay-Weber syndrome, McCune-Albright syndrome, and Beckwith-Wiedemann syndrome (BWS).1 The incidence of IH is ∼1/86 000 live births,3 with a male:female ratio of 1:2.1 The aetiology of IH is unknown. A number of different chromosomal anomalies, including diploid-triploid mosaicism and trisomy 18 mosaicism, have been identified, and the causes of IH are likely to be heterogeneous.2 It has been suggested that IH may be one end of the spectrum of phenotypes of BWS, linked to the chromosomal locus 11p15.1 Here we report a case of apparently isolated hemihypertrophy in one of a pair of monozygotic twins, with paternal uniparental disomy in an area of the 11p15 locus associated with BWS. The subjects of the study are a pair of female twins, one of whom (twin 2) has hemihypertrophy. Twin 1 has a normal physical appearance. The twins were born at 36 weeks of gestation by normal vaginal delivery. Twin 1 weighed 2730 g and twin 2 weighed 3205 g. Apgar score at birth was 10 for each girl. Twin 1 fed well and gained weight as expected with no neonatal problems. Twin 2 initially failed to pass meconium and was intolerant of feeds. She was noted to have hemihypertrophy affecting the right leg and arm and an ultrasound scan showed enlargement of the right kidney. She was given a glycerine suppository and passed meconium …

Huntington disease (HD) belongs to the group of neurodegenerative disorders characterized by unstable expanded trinucleotide repeats. In the case of HD, the expansion of a CAG repeat occurs in the IT15 gene. The detection of the expanded CAG repeats has usually involved the electrophoretic separation of polymerase chain reaction (PCR) amplification products using conventional agarose and acrylamide gel electrophoresis. We have undertaken the comparative analysis of sizing CAG repeats of the IT15 gene using radioactive and fluorescent PCR amplification, and the subsequent separation of these products by slab gel and capillary electrophoresis. The assays have been performed on both cloned and sequenced CAG repeats, as well as genomic DNA from HD patients with a wide range of repeat lengths. The mobility of the CAG repeat amplification products of the IT15 gene is greater using capillary electrophoresis compared to slab gel electrophoresis. The analysis of 40 DNA samples from HD patients indicates that the mobility difference increases with the length of the repeat. However, we have devised an allele ladder for sizing the CAG repeats. This ladder provides a mandatory internal calibration system for diagnostic purposes and enables the confident use of either capillary or slab gel electrophoresis for sizing HD alleles.

AIMS:To establish and validate a polymerase chain reaction (PCR)-based diagnostic test in New Zealand, which enables the number of CAG repeats present in the Huntington's disease (HD) gene to be determined with speed and accuracy. To develop procedures for reporting and counselling probands and families.METHODS:The analysis of the CAG repeat region in Huntington's disease and normal chromosomes involved PCR amplification of genomic DNA using either the incorporation of radioactive deoxynucleotides or fluorescent oligonucleotide primers.RESULTS:The molecular analysis of the CAG repeat sequence in the Huntington's disease gene of over 100 New Zealand individuals has been performed. Huntington's disease chromosomes contained 37-70 (median 44) repeats whereas normal chromosomes contained 9-27 (median 18) repeats. Six individuals from three families had an allele in the intermediate range (30-36 repeats). Instability of the CAG repeat upon transmission from generation to generation was also observed. A comparison of the results obtained using radioactive and fluorescent assays indicates that while both methods are reliable, the latter method is more rapid and allows for automation to be incorporated in the scoring of allele sizes.CONCLUSIONS:Our analysis of Huntington's disease alleles has shown a profile of CAG repeat lengths that is consistent with those reported internationally. In addition, reporting and counselling procedures have been established for presymptomatic testing of Huntington's disease in New Zealand.

UVB radiation is known to trigger the block of DNA replication and transcription by forming cyclobutane pyrimidine dimer (CPD), which results in severe skin damage. CPD photolyase, a kind of DNA repair enzyme, can efficiently repair CPDs that are absent in humans and mice. Although exogenous CPD photolyases have beneficial effects on skin diseases, the mechanisms of CPD photolyases on the skin remain unknown. Here, this study prepared CPD photolyase nanoliposomes (CPDNL) from Antarctic Chlamydomonas sp. ICE-L, which thrives in harsh, high-UVB conditions, and evaluated their protective mechanisms against UVB-induced damage in mice. CPDNL were optimized using response surface methodology, characterized by a mean particle size of 105.5 nm, with an encapsulation efficiency of 63.3%. Topical application of CPDNL prevented UVB-induced erythema, epidermal thickness, and wrinkles in mice. CPDNL mitigated UVB-induced DNA damage by significantly decreasing the CPD concentration. CPDNL exhibited antioxidant properties as they reduced the production of reactive oxygen species (ROS) and malondialdehyde. Through activation of the NF-κB pathway, CPDNL reduced the expression of pro-inflammatory cytokines including IL-6, TNF-α, and COX-2. Furthermore, CPDNL suppressed the MAPK signaling activation by downregulating the mRNA and protein expression of ERK, JNK, and p38 as well as AP-1. The MMP-1 and MMP-2 expressions were also remarkably decreased, which inhibited the collagen degradation. Therefore, we concluded that CPDNL exerted DNA repair, antioxidant, anti-inflammation, and anti-wrinkle properties as well as collagen protection via regulation of the NF-κB/MAPK/MMP signaling pathways in UVB-induced mice, demonstrating that Antarctic CPD photolyases have the potential for skincare products against UVB and photoaging.

Journal Article Two dinucleotide repeat polymorphisms at the DMD locus Get access S.C. King, S.C. King Search for other works by this author on: Oxford Academic PubMed Google Scholar P.M. Stapleton, P.M. Stapleton 1DNA Diagnostics LtdPO Box 5739, Auckland, New Zealand Search for other works by this author on: Oxford Academic PubMed Google Scholar A.P. Walker, A.P. Walker 2ICRF Laboratories, Institute of Molecular Medicine, John Radcliffe HospitalHeadington, Oxford OX3 9DU, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar D.R. Love D.R. Love * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 3, Issue 3, March 1994, Page 523, https://doi.org/10.1093/hmg/3.3.523 Published: 01 March 1994

Journal Article Two dinucleotide repeat polymorphisms at the DMD locus Get access S.C. King, S.C. King Search for other works by this author on: Oxford Academic PubMed Google Scholar P.M. Stapleton, P.M. Stapleton 1DNA Diagnostics LtdPO Box 5739, Auckland, New Zealand Search for other works by this author on: Oxford Academic PubMed Google Scholar A.P. Walker, A.P. Walker 2ICRF Laboratories, Institute of Molecular Medicine, John Radcliffe HospitalHeadington, Oxford OX3 9DU, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar D.R. Love D.R. Love * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 3, Issue 3, March 1994, Page 523, https://doi.org/10.1093/hmg/3.3.523 Published: 01 March 1994

Using DNA fingerprinting we estimated the reproductive success of 49 adult birds belonging to 16 breeding groups of the sexually monomorphic brown skua (Catharacta lonnbergi) from the Chatham Islands (New Zealand). This population has a variable mating system, breeding in both monogamous and polyandrous groups. The parentage of 45 chicks produced over three breeding seasons was unequivocally determined using the multilocus probes 33.15 and 33.6. We found no evidence of either extra-pair or extra-group fertilization and there was no evidence to suggest egg dumping by females in any breeding group. Consequently, in the case of pairs, parentage of all chicks was assigned to the resident adult birds. In addition, band sharing analysis indicated that members of communal groups were not close relatives. In the 10 communally breeding groups examined, multiple paternity within a clutch was recorded on two of the 12 occasions in which two chicks were reared. Analysis of the parentage of offspring belonging to different groups, from different years, demonstrated that the number of chicks produced by some adult males varied considerably between seasons. In contrast, the reproductive success of other individuals was constant; for example, one male produced two chicks in each of the three seasons it was studied, while other males in communal groups did not produce any chicks during the course of this study. Fitness is a lifetime parameter, and any assessment of it requires studies over at least the average lifetime of an individual. The findings presented in this study suggest that, for brown skuas, there are significant differences in the reproductive success of some adult males in different breeding seasons. These results indicate that estimates of reproductive fitness based on only a single breeding season's data can be seriously inaccurate. Should temporal changes in paternity (and/or maternity) be shown to be common phenomena in other species, then such results would have major implications for the interpretation of parentage studies.

DNA fingerprinting was used to assign the sex of individuals of brown skua (Catharacta lonnbergi). A population of this sexually monomorphic sea bird is found on the Chatham Islands off the coast of New Zealand. A large proportion of the individuals within this population breed communally. Hybridization of the DNA fingerprinting probe pV47-2 to genomic DNA from brown skua revealed several high molecular weight DNA fragments present exclusively in females. This finding is consistent with the assignment of sex based on the available morphometric and behavioral data. We conclude that these restriction fragments are located on the W chromosome. Consequently, the presence of these fragments can be used to identify female adults and chicks. We recorded a biased sex ratio among adult birds in breeding territories, with almost twice as many males as females. In contrast, the sex ratio among chicks approximates 1:1. These results are discussed in relation to contemporary ideas about the evolution of communal breeding.