ABSTRACT

Thehuman~-globingenehasbeenwellcharacterizedatthemolecularlevel.Itispartofa clusterofsixrelatedgenesandpseudogenesonchromosome11,anditconsistsofthreeexons andtwointronsspanninglessthan2kilobases(kb)(14).Asfarastargetsizeisconcerned, however,theorganizationofthegeneisunimportantbecausetheassayscreensdirectlyfornew mutationswithspecificaminoacidreplacements.Todate,theassayhasbeenperformedwith antibodiesagainstthreedifferentvarianthemoglobins,hemoglobinsSandC,asdescribed above,aswellashemoglobinsanJose(15),thatrequirenotonlyamutationataspecificbasein thecodingsequencebutaspecificchangeatthatbase.Thus,thetargetsizeforthisassay consistsofasinglebase,andeventhenonlyoneofthreepossiblebasechangesaredetectable. Recently,theassayhasbeenextendedtoasecondtypeofmutantbyutilizingantibodiesagainst aninheritedabnormalhemoglobin,hemoglobinLeiden,avariantthatrequiresthein-framedeletion ofonecodonfromthecodingsequence(15).