caa a22 4500 397574878 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199606 xx s 000 0 eng 10.1093/hmg/5.6.727 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.6.727 Population Screening at the FRAXA and FRAXE Loci: Molecular Analyses of Boys with Learning Difficulties and Their Mothers [Elektronische Daten] [Anna Murray, Sheila Youings, Nick Dennis, Lorinda Latsky, Paul Linehan, Nicky McKechnie, James Macpherson, Michelle Pound, Patricia Jacobs] Preliminary results on a large population-based molecular survey of FRAXA and FRAXE are reported. All boys with unexplained learning difficulties are eligible for inclusion in the study and data are presented on the first 1013 tested. Individuals were tested for the number of trinucleotide repeats at FRAXA and FRAXE and typed for four flanking microsatellite markers. Mothers of 760 boys were tested to determine the stability of the FRAXA and FRAXE repeats during transmission and to provide a population of control chromosomes. The frequency of FRAXA full mutations was 0.5%, which gives a population frequency of 1 in 4994, considerably less than previous reports suggest. No FRAXE full mutations were detected, confirming the rarity of this mutation. In the boys' X chromosomes, we detected one FRAXA premutation with 152 repeats and one putative FRAXE premutation of 87 repeats. No full or premutations were seen in the control chromosomes. A significant excess of intermediate alleles at both FRAXA and FRAXE was detected in the boys' X chromosomes by comparison with the maternal control chromosomes. This suggests that relatively large unmethylated repeats of sizes 41-60 for FRAXA and 31-60 for FRAXE may play some role in mental impairment. No instability was found in transmissions of minimal or common alleles in either FRAXA or FRAXE, but we saw two possible instabilities in transmission of FRAXA and two definite instabilities in transmission of FRAXE among 43 meioses involving intermediate or premutation sized alleles. We found no linkage disequilibrium between FRAXA and FRAXE but did find significant linkage disequilibrium between large alleles at FRAXE and allele 3 at the polymorphic locus DXS1691 situated 5 kb distal to FRAXE. © 1996 Oxford University Press Murray Anna Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Youings Sheila Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Dennis Nick Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut Latsky Lorinda Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Linehan Paul CRC Epidemiology Research Group, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut McKechnie Nicky Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut Macpherson James Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Pound Michelle Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Jacobs Patricia Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut Human Molecular Genetics Oxford University Press 5/6(1996-06), 727-735 0964-6906 5:6<727 1996 5 hmg https://doi.org/10.1093/hmg/5.6.727 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.6.727 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Murray Anna Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 700 1- Youings Sheila Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 700 1- Dennis Nick Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut NATIONALLICENCE 700 1- Latsky Lorinda Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 700 1- Linehan Paul CRC Epidemiology Research Group, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut NATIONALLICENCE 700 1- McKechnie Nicky Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, Hampshire SO16 5YA, UK aut NATIONALLICENCE 700 1- Macpherson James Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 700 1- Pound Michelle Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 700 1- Jacobs Patricia Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/6(1996-06), 727-735 0964-6906 5:6<727 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford