SicklecelldiseaseSicklecelldiseaseiscausedbythesubstitutionofasingleaminoacidinthehemoglobinproteinofredbloodcells.Whentheoxygencontentofanaffectedindividual'sbloodislow(athighaltitudesorunderphysicalstree,forinstance),thesicklecellhemolgobinmoleculescrystallizebyaggregatingintolongrods.thecrystalsdeformtheredcellsintoasickleshape.Sicklingofthecells,inturn,canleadtoothersymptoms.Themutlipleeffectsofadoubledoesofthesicklecellalleleareanexampleofpleiotropy.Thenon-sicklecellcounterpartofthesicklecellalleleisinfactonlyincompletelydominanttothesicklecellalleleattheleveloftheorganism.Heterozygotes--carriersofasinglesicklecellallele--aresaidtohavesicklecelltrait.Suchpeopleareusuallyhealthy,althoughafractionsuffersomesymptomsofsicklecelldiseasewhenthereisanextendedreductionofbloodoxygen.Sickle-celldiseaseorsickle-cellanaemia(oranemia)isablooddisordercharacterizedbyredbloodcellsthatassumeanabnormal,rigid,sickleshape.Sicklingdecreasesthecells'flexibilityandresultsintheirrestrictedmovementthroughbloodvessels,deprivingdownstreamtissuesofoxygen.Thediseaseischronicandlifelong:individualsaremostoftenwell,buttheirlivesarepunctuatedbyperiodicpainfulattacksandariskofvariousothercomplications.Lifeexpectancyisshortened,witholderstudiesreportinganaveragelifeexpectancyof42and48yearsformalesandfemales,respectively.[1]Sickle-celldiseaseoccursmorecommonlyinpeople(ortheirdescendants)frompartsofsub-SaharanAfrica,wheremalariaisorwascommon,butitalsooccursinpeopleofotherethnicities.Thisisbecausethosewithoneortwoallelesofthesickle-celldiseaseareresistanttomalariasincethesickleredbloodcellsarenotconducivetotheparasites-inareaswheremalariaiscommon,thereisasurvivalvalueincarryingthesickle-cellgenes.HistoryThiscollectionofclinicalfindingswasunknownuntiltheexplanationofthesicklecellsin1904bytheChicagocardiologistandprofessorofmedicineJamesB.Herrick(1861-1954)whoseinternErnestEdwardIrons(1877-1959)found"peculiarelongatedandsickleshaped"cellsinthebloodofWalterClementNoel,a20yearoldfirstyeardentalstudentfromGrenadaafterNoelwasadmittedtotheChicagoPresbyterianHospitalinDecember1904sufferingfromanaemia.Noelwasreadmittedseveraltimesoverthenextthreeyearsfor"muscularrheumatism"and"biliousattacks".NoelcompletedhisstudiesandreturnedtothecapitalofGrenada(St.George's)topracticedentistry.Hediedofpneumoniain1916andisburiedintheCatholiccemeteryatSauteursinthenorthofGrenada.[14]Thediseasewasnamed"sickle-cellanaemia"byVernonMasonin1922.Inretrospectsomeelementsofthediseasehadbeenrecognizedearlier:apaperintheSouthernJournalofMedicalPharmacologyin1846describedtheabsenceofaspleenintheautopsyofarunawayslave.TheAfricanmedicalliteraturereportedthisconditioninthe1870swhereitwasknownlocallyasogbanjes("childrenwhocomeandgo")becauseoftheveryhighinfantmortalityratecausedbythiscondition.Ahistoryoftheconditiontrackedreportsbackto1670inoneGhanaianfamily.[15]Also,thepracticeofusingtarsoaptocoverblemishescausedbysickle-cellsoreswasprevalentintheAfricanAmericancommunity.[citationneeded]LinusPaulingandcolleagueswerethefirst,in1949,todemonstratethatsicklecelldiseaseoccursasaresultofanabnormalityinthehaemoglobinmolecule.Thiswasthefirsttimeageneticdiseasewaslinkedtoamutationofaspecificprotein,amilestoneinthehistoryofmolecularbiology.Theoriginofthemutationthatledtothesickle-cellgenewasinitiallythoughttobeintheArabianpeninsula,spreadingtoAsiaandAfrica.Itisnowknown,fromevaluationofchromosomestructures,thattherehavebeenatleastfourindependentmutationalevents,threeinAfricaandafourthineitherSaudiArabiaorcentralIndia.[16]Theseindependenteventsoccurredbetween3,000and6,000generationsago,approximately70-150,000years.