Referee report. For: The FRAXA and FRAXE allele repeat size of boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) [version 2; peer review: 1 approved, 1 approved with reservations]

Randi J. Hagerman
2020
The FRAXA and FRAXE alleles of the FMR1 and FMR2 genes located on the X chromosome contain varying numbers of trinucleotide repeats. Large numbers of repeats at FRAXA (full mutations) manifest as Fragile X syndrome, associated with mental impairment that affects males more severely. In this paper, we present the dataset of frequencies of FRAXA and FRAXE repeat size extracted from DNA samples collected from boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). DNA data
more » ... re extracted from samples collected in ALSPAC clinics from several types of samples: cord blood, venepuncture blood taken at 43 months, 61 months, seven years or nine years. The DNA was amplified at FRAXA and FRAXE using fluorescent PCR in the Wessex Regional Genetics Laboratory, Salisbury District Hospital. The mean repeat size for FRAXA is 28.92 (S.D. 5.44), the median 30 and the range 8 to 68. There were particularly high numbers of boys with repeat sizes of 20 (10.67%) and 23 (7.35%). The mean repeat size for FRAXE is 17.41 (S.D. 3.94), with median of 16 and range of 0 to 61. There is a relatively high degree of variation of the FRAXA repeat size particularly and we suggest the extensive data available from the ALSPAC study opens up areas of research into understanding phenotypes associated with relatively unexplored repeat sizes. This could be particularly interesting for the lower repeat sizes occurring with high frequency at FRAXA in this population. As the data can be linked to exposures and phenotypes, it will provide a resource for researchers worldwide. PubMed Abstract | Publisher Full Text | Free Full Text Chandrasekara B, Wijesundera S, Chong SS, et al.: Prevalence of Fragile X Syndrome among children receiving special education and carrier states in first degree relatives. Ceylon Med J. 2017; 62(2): 92-96. PubMed Abstract | Publisher Full Text Cornish KM, Li L, Kogan CS, et al.: Age-dependent cognitive changes in carriers of the fragile X syndrome. Cortex. 2008; 44(6): 628-636. PubMed Abstract | Publisher Full Text Crawford DC, Meadows KL, Newman JL, et al.: Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large, ethnically diverse, special education-needs population. Am J Hum Genet. 1999; 64(2): 495-507. PubMed Abstract | Publisher Full Text | Free Full Text Ennis S, Murray A, Youings S, et al.: An investigation of FRAXA intermediate allele phenotype in a longitudinal sample. Ann Hum Genet. 2006; 70(Pt 2): 170-180. PubMed Abstract | Publisher Full Text Fraser A, Macdonald-Wallis C, Tilling K, et al.: Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int J Epidemiol. 2013; 42(1): 97-110. PubMed Abstract | Publisher Full Text | Free Full Text Golding J, Pembrey M, Jones R, et al.: ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatr Perinat Epidemiol. 2001; 15(1): 74-87. PubMed Abstract | Publisher Full Text Hagerman RJ, Leavitt BR, Farzin F, et al.: Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet. 2004; 74(5): 1051-1056. PubMed Abstract | Publisher Full Text | Free Full Text Hagerman RJ, Leehey M, Heinrichs W, et al.: Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology. 2001; 57(1): 127-130. PubMed Abstract | Publisher Full Text Jones RW, Ring S, Tyfield L, et al.: A new human genetic resource: a DNA bank established as part of the Avon longitudinal study of pregnancy and childhood (ALSPAC). Eur J Hum Genet. 2000; 8(9): 653-60. PubMed Abstract | Publisher Full Text Knight SJ, Flannery AV, Hirst MC, et al.: Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell. 1993; 74(1): 127-134. PubMed Abstract | Publisher Full Text Knight SJ, Ritchie RJ, Chakrabarti L, et al.: A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom. Am J Hum Genet. 1996; 58(5): 906-13. PubMed Abstract | Free Full Text Kraan CM, Bui QM, Field M, et al.: FMR1 allele size distribution in 35,000 males and females: a comparison of developmental delay and general population cohorts. Genet Med. 2018; 20(12): 1627-1634. PubMed Abstract | Publisher Full Text Lubs HA: A marker X chromosome. Am J Hum Genet. 1969; 21(3): 231-44. PubMed Abstract | Free Full Text Macpherson J, Waghorn A, Hammans S, et al.: Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia. Hum Genet. 2003; 112(5-6): 619-620. PubMed Abstract | Publisher Full Text Murray A, Youings S, Dennis N, et al.: Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers. Hum Mol Genet. 1996; 5(6): 727-735. PubMed Abstract | Publisher Full Text Office of Population Censuses and Surveys: Standard occupation classification. London: HMS, 1990. Reference Source Pembrey ME, Barnicoat AJ, Carmichael B, et al.: An assessment of screening strategies for fragile X syndrome in the UK. Health Technol Assess. 2001; 5(7): 1-95. PubMed Abstract | Publisher Full Text Pieretti M, Zhang FP, Fu YH, et al.: Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991; 66(4): 817-822. PubMed Abstract | Publisher Full Text Sutherland GR: Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science. 1977; 197(4300): 265-266. PubMed Abstract | Publisher Full Text Sutherland GR: Heritable fragile sites on human chromosomes. III. Detection of fra(X)(q27) in males with X-linked mental retardation and in their female relatives. Hum Genet. 1979; 53(1): 23-27. PubMed Abstract | Publisher Full Text Youings SA, Murray A, Dennis N, et al.: FRAXA and FRAXE: the results of a five year survey. J Med Genet. 2000; 37(6): 415-421. PubMed Abstract | Publisher Full Text | Free Full Text
doi:10.21956/wellcomeopenres.17209.r37690 fatcat:7zlv2y4thrhwplvkvoxyb2pfja