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The novel allele, HLA-A*1115, was identified in an 'Educational Scheme' sample (ED03/03 - from a north-western European Caucasoid blood donor) distributed by the UK National External Quality Assessment Schemes for Histocompatibility and Immunogenetics. ED03/03 was typed by serology, the polymerase chain reaction using sequence-specific primers and sequence-based typing. A*1115 is most similar to A*110101 with a single mismatch (G to C) at constant position 565, leading to a conservative amino acid change from valine (GTG) to leucine (CTG) at codon 165 in the alpha(2) domain. This substitution has not been reported for any other HLA class I allele so far. The HLA-A*1115-bearing haplotype was B*350101; Cw*040101; DRB1*140101; DRB3*020201; DQA1*010401; DQB1*0503; DPA1*0103/07; DPB1*030101. Extensive serological typing indicated that this allele essentially encodes a 'normal' HLA-A11 specificity.

We report here the identification of a novel DRB4*01 allele, DRB4*010304, found in a patient waiting for a liver transplantation. The new allele was detected during a routine DNA-based HLA typing. Sequencing confirmed that the new allele is identical to DRB4*01030101 at exon 2 except for position 216 where the new allele has a T instead of a C.

We have identified a new HLA-B*15 allele (B*1569) by polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing (SBT). This novel allele was found in a 67-year-old white Caucasian male and differs from HLA-B*1503 at 3 positions. The nucleotide substitutions at positions 544, 559 and 560 result in amino acid changes at codon 158 from GCC (alanine) to ACC (threonine), and at codon 163 from CTG (leucine) to ACG (threonine).

We have identified a new HLA-B*39 allele through polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing of exons 2 and 3. This novel allele was identified in three HLA-identical siblings of Turkish origin. This allele only differs from HLA-B*3903 at a unique single nucleotide substitution (T for C) at position 365 in exon 3 which results in an amino acid change in codon 98 of methionine (ATG) to threonine (ACG). The sequencing enabled the development of a monospecific PCR-SSP reaction which can be used to discriminate between HLA-B*3924 and other B*39 alleles.

We report here a new allele, B*15012, identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT). B*15012 differs to B*15011 (previously named B*1501) by a single nucleotide, at position 435 of codon 120. B*15011 encodes AAG and B*15012 encodes AAA at codon 120, this difference does not result in an amino acid change.

We have identified a null HLA-A*02 allele, HLA-A*0232N, by using a combination of serology, flow cytometry, polymerase chain reaction using sequence-specific primers (PCR-SSP) and full-length sequencing. The null HLA-A2 allele was identified in an Asian individual originally typed by serology as an apparently homozygous HLA-A3, B51. Subsequent genotyping by PCR-SSP identified the genotype as HLA-A*0201, *0301, B*51, Cw*1402. The serological type and lack of detectable HLA-A2 was confirmed using monoclonal antibody typing reagents. Flow cytometry studies failed to identify any cell surface HLA-A2 expression on the patient's peripheral blood lymphocytes. Genotyping using a PCR-SSP set designed to detect null alleles revealed the mutation had not been previously described. Full-length sequencing of the allele identified an allele which was subsequently named HLA-A*0232N. This allele is identical to HLA-A*0201 except for a novel point mutation (T for C) at position 493 which creates a premature stop codon. The sequencing enabled the development of a monospecific A*0232N PCR-SSP reaction which was used to screen 973 DNA samples: no further examples of A*0232N were identified.

We have identified a variant HLA-B allele, B*0808N, segregating through two generations of healthy individuals, whilst HLA typing the family of a bone marrow patient. Serological typing identified a disparity between the father (A1, A3 B7 DR7) and the brother (A1, A2 B56 DR1, DR7) of the patient. Low/medium resolution polymerase chain reaction using sequence-specific primers (PCR-SSP) revealed a B*08 allele undetectable by serological methods. High resolution DNA typing by polymerase chain reaction-sequencing based typing (PCR-SBT), revealed a nucleotide deletion at position 131 (C) in exon 3, the only difference between the new allele and B*0801. The deletion results in a frame shift in the protein coding sequence, introducing a premature termination codon (TGA) in exon 4. Although a B*08 allele is present in these individuals, the deletion prevents correct expression of the antigen on the cell surface.

We have identified an HLA-A11 variant allele, A*1105, segregating in a Caucasoid family. The variant antigen expressed by this allele failed to cross-react with most Caucasoid anti-HLA-A11 antisera tested. Sequencing based typing has been used to characterize this new allele and this showed that it has a novel mutation at a polymorphic position (502) in exon 3. In comparison with A*1101, the mutation (A-->G) results in an amino acid change from positively-charged lysine to negative glutamate and this may explain the altered HLA-A11 serological profile exhibited by this antigen. The new allele was found in a patient with acute lymphoid leukaemia (ALL), her father and two siblings.

A novel HLA-B51 allele, B*5113, was identified in a Kolla Amerindian individual from North-West Argentina. HLA-B*5113 differs from B*51011 by two nucleotide substitutions, one synonymous, the other nonsynonymous. The resulting amino acid difference at residue 116 in the HLA-B molecule's peptide binding site is likely to affect the nature of the peptides which bind to this molecule. The finding of this novel allele supports previous findings of increased diversity at HLA-B in Amerindian groups.

We have identified a variant HLA-C allele, Cw*0805, in DNA isolated from a blood sample used in the UK National External Quality Assessment Scheme for Histocompatibility and Immunogenetics. The DNA was initially typed by PCR-SSP and PCR-SBT as Cw*0802, 1602 with a single mismatch in exon 2 of one of the alleles. The two HLA-C alleles were separated by locus- and allele-specific PCRs and sequencing analysis showed that the Cw*0802 allele was variant in this sample, with a single mismatch in exon 2 at position 289.

Titin provides a molecular blueprint for muscle sarcomere assembly, and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus, the aim of this study was to investigate whether the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n=137) and marathon personal best time in male marathon runners (MR; n=141). Fascicle length of the vastus lateralis was assessed in vivo using B‐mode ultrasonography at 50% of muscle length in RA. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real‐time polymerase chain reaction. Vastus lateralis fascicle length was 10.4% longer in CC homozygotes, those carrying two copies of the C‐allele, than CT heterozygotes (P=.003) in RA. In the absence of any TT homozygotes, reflective of the low T‐allele frequency within Caucasian populations, it is unclear whether fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P=.500), although within the MR group, the T‐allele carriers demonstrated marathon personal best times 2 minutes 25 seconds faster than CC homozygotes (P=.020). These results suggest that the T‐allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men. [ABSTRACT FROM AUTHOR]