TY - JOUR
T1 - The pattern of factor IX germ-line mutation in asians is similar to that of caucasians
AU - Bottema, Cynthia D.K.
AU - Ketterling, Rhett P.
AU - Yoon, Hong Sup
AU - Sommer, Steve S.
PY - 1990/11
Y1 - 1990/11
N2 - To begin documenting the pattern of germ-line mutations in different human races, we have delineated the mutation in nine Korean families with hemophilia B by direct genomic sequencing of the regions of likely functional significance in the factor IX gene. An evaluation of these mutations in combination with previously described point mutations in the factor IX gene of Asians indicates that transitions predominate followed by transversions and microdeletions/insertions. Transitions at the dinucleotide CpG are a dramatic hot spot of mutation. This pattern of mutation is very similar to that observed in Caucasians with hemophilia B, despite the many differences between Asians (mostly Koreans) and Caucasians in diet, environment and cultural life-styles. The similarity may reflect the predominance of endogenous processes or ubiquitous mutagens rather than specific mutagens in the environment. The following additional conclusions emerge: (1) The missense mutations in Asians occur at evolutionarily conserved amino acids. When combined with the previous data this makes it likely that more than two-thirds of the missense mutations which could possibly occur at nonconserved amino acids do not cause hemophilia B. (2) Surprisingly, a change in the sixth base of the intron 2 donor splice-junction sequence is associated with severe disease in HB 74/77. (3) Direct carrier testing of nine Korean families demonstrates that the stability of DNA at ambient temperature in blood with the anticoagulant ACD solution B makes it feasible for a diagnostic laboratory to perform such testing at a distance of 7,000 miles. Carrier testing revealed that the mutation in HB78 arose in his mother's germ-line. (4) A search for informative polymorphic alleles in Koreans reveals that the HhaI polymorphism is informative in about one-third of females.
AB - To begin documenting the pattern of germ-line mutations in different human races, we have delineated the mutation in nine Korean families with hemophilia B by direct genomic sequencing of the regions of likely functional significance in the factor IX gene. An evaluation of these mutations in combination with previously described point mutations in the factor IX gene of Asians indicates that transitions predominate followed by transversions and microdeletions/insertions. Transitions at the dinucleotide CpG are a dramatic hot spot of mutation. This pattern of mutation is very similar to that observed in Caucasians with hemophilia B, despite the many differences between Asians (mostly Koreans) and Caucasians in diet, environment and cultural life-styles. The similarity may reflect the predominance of endogenous processes or ubiquitous mutagens rather than specific mutagens in the environment. The following additional conclusions emerge: (1) The missense mutations in Asians occur at evolutionarily conserved amino acids. When combined with the previous data this makes it likely that more than two-thirds of the missense mutations which could possibly occur at nonconserved amino acids do not cause hemophilia B. (2) Surprisingly, a change in the sixth base of the intron 2 donor splice-junction sequence is associated with severe disease in HB 74/77. (3) Direct carrier testing of nine Korean families demonstrates that the stability of DNA at ambient temperature in blood with the anticoagulant ACD solution B makes it feasible for a diagnostic laboratory to perform such testing at a distance of 7,000 miles. Carrier testing revealed that the mutation in HB78 arose in his mother's germ-line. (4) A search for informative polymorphic alleles in Koreans reveals that the HhaI polymorphism is informative in about one-third of females.
UR - http://www.scopus.com/inward/record.url?scp=0025075346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025075346&partnerID=8YFLogxK
M3 - Article
C2 - 2220823
AN - SCOPUS:0025075346
SN - 0002-9297
VL - 47
SP - 835
EP - 841
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -