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2.1 12 Using genetic diagrams – 2 By the end of this spread, you should be able to … 1 Use genetic diagrams to solve problems involving codominance. Sickle-cell anaemia Key definition Alleles are codominant if they both contribute to the phenotype. Parent genotypes Gametes HAHS HA HS HAHS HA HS HA HS HA HAHA normal HAHS carrier HS HSHA carrier HSHS sickle-cell anaemia 25% normal haemoglobin 50% carrier 3ICKLECELLANAEMIAWASTHElRSTHUMANDISEASETOBEUNDERSTOODATTHEMOLECULARLEVEL s !LLINDIVIDUALSWITHTHEDISEASEHAVETHESAMEMUTATION s 4HEB-strands of haemoglobin differ by one amino acid at position 6. s )NNORMALHAEMOGLOBINGLUTAMICACIDISATPOSITIONBUTINSICKLECELLHAEMOGLOBIN VALINEISPRESENTINSTEAD s 7HENTHISABNORMALHAEMOGLOBINISDEOXYGENATEDITISNOTSOLUBLEANDBECOMES crystalline and aggregates into more linear and less globular structures. This deforms THEREDBLOODCELLSMAKINGTHEMINmEXIBLEANDOFTENSICKLESHAPEDANDUNABLETO SQUEEZETHROUGHCAPILLARIES s !FTERMANYCYCLESOFOXYGENATIONANDDEOXYGENATIONSOMECELLSBECOMEIRREVERSIBLY sickled. Some are destroyed. s )FENOUGHSICKLECELLSBECOMELODGEDINCAPILLARIESBLOODmOWISIMPEDED/RGANS PARTICULARLYBONESDONOTRECEIVEENOUGHOXYGENLEADINGTOAPAINFULCRISIS s %VENTUALLYORGANSESPECIALLYHEARTLUNGSANDKIDNEYSBECOMEDAMAGED s 4HEGENOTYPEOFPEOPLEWITHNORMALHAEMOGLOBINCANBEDENOTEDASHAHA. s 4HEGENOTYPEOFPEOPLEWITHSICKLECELLANAEMIAISHsHs. s 4HEGENOTYPEOFSYMPTOMLESSHETEROZYGOTESISHAHs. 25% sicklecell anaemia Key: HA allele for normal haemoglobin HS allele for abnormal haemoglobin Figure 3 Genotypes and phenotypes of offspring of two parents, both HETEROZYGOUSFORSICKLECELLDISEASE Figure 1 3ICKLEDANDREDBLOODCELLS Figure 2 0ATIENTWITHSICKLECELLANAEMIA EXPERIENCINGAPAINFULCRISIS )NHETEROZYGOTESREDBLOODCELLSAREMADEINTHEBONEMARROWWITHHALFTHEIR HAEMOGLOBINNORMALANDHALFSICKLED4HEPRESENCEOFNORMALHAEMOGLOBINPREVENTS SICKLINGINTHEREDCELLSWHENTHEYAREINTHECIRCULATIONANDDEOXYGENATED4HUS HETEROZYGOTESARESYMPTOMLESSCARRIERSANDATWHOLEORGANISMLEVELTHISCONDITIONCOULD BECONSIDEREDTOBERECESSIVE(OWEVERATTHEMOLECULARANDCELLULARLEVELBECAUSE BOTHALLELESCONTRIBUTETOTHEPHENOTYPEASOBSERVEDINREDBLOODCELLSITISCODOMINANT What are the possible genotypes and phenotypes of offspring of two parents, both carriers of sickle-cell disease? 7ECANSEEFROM&IGURETHATWEEXPECTTOHAVENORMALHAEMOGLOBINTOBE HETEROZYGOUSCARRIERSANDTOHAVESICKLECELLANAEMIA Roan cattle /NEOFTHEGENESFORCOATCOLOURINSHORTHORNCATTLEHASTWOALLELESCR codes for red hairs and CW codes for white hairs. s (OMOZYGOUSINDIVIDUALSWITHGENOTYPECRCRHAVEREDCHESTNUTCOATS 126 178 biology.U2 M1.indd 126 3/10/08 11:01:59 Module 1 Cellular control Using genetic diagrams – 2 s (OMOZYGOUSINDIVIDUALSWITHGENOTYPECWCWHAVEWHITECOATS s (ETEROZYGOTESGENOTYPECRCWHAVEREDANDWHITEHAIRSANDTHECOATISROAN )FREDANDWHITESHORTHORNCATTLEAREINTERBREDTHENALLTHEOFFSPRINGAREROANnAMIXTURE of red and white. )FTWOROANSHORTHORNCATTLEAREINTERBREDTHENTHEPROBABLEPHENOTYPESARERED ROANANDWHITE&IGURE STRETCH and CHALLENGE Patients with sickle-cell anaemia can be treated by blood transfusions about every three months. Some patients have been treated with chemotherapy. They are given hydroxyurea that causes an increase in fetal haemoglobin formation and produces an improvement in red blood cell function. Some patients have been treated with bone marrow transplants, although this is reserved for severely affected patients as there is a risk of graft-versus-host reaction. Questions A Explain why an increase in fetal haemoglobin improves red cell function in sickle-cell patients. (Hint: revisit AS work on transport in animals.) B Suggest what is meant by ‘graft-versus-host reaction’. (Hint: revisit AS work on the immune system.) C Suggest why blood transfusions are given every three months. (Hint: revisit AS work on transport in animals.) There are various ways to diagnose sickle-cell disease. A blood smear can be exposed to very low oxygen concentrations to see if red cells become sickled. However, this can give false positives for carriers, as under these laboratory conditions, red blood cells from heterozygotes may also sickle. A more accurate diagnosis involves electrophoresis of haemoglobin. A sample of extracted haemoglobin is placed in a well in an electrophoresis gel and a buffer solution added. Electrodes are placed at either end and the protein migrates towards the positive electrode, according to the overall electric charge on the protein. Glutamic acid has a negative charge and valine is neutral. Figure 4 Red shorthorn bull Parental phenotypes Cow ( ) Red White Genotypes CRCR CWCW CR CW Gametes Offspring genotypes All CRCW Offspring phenotypes All roan Figure 5 Genetic diagram of cross between red shorthorn cow and white shorthorn bull Parent phenotypes Roan Roan Parent genotypes CWCR CWCR Gametes An analysis of the gene encoding the B-globulin from the individual’s DNA can diagnose the presence of the mutation. This can also be done on fetal cells obtained prenatally by chorionic villus sampling or amniocentesis. Question E Explain why cells such as skin cells, and not red blood cells, are used for DNA analysis for the presence of a mutated B-globulin gene. Questions 1 !SHORTHORNBULLISRUNWITHAHERDOFREDSHORTHORNCOWS/FTHECALVESPRODUCEDINTHE lRSTYEARAREREDANDAREROAN7HATISTHEGENOTYPEANDPHENOTYPEOFTHEBULL 2 $UCKSOFTHEBREEDCALLED3WEDISHBLUEHAVEGREYPLUMAGE)FTWO3WEDISHBLUE DUCKSMATESOMEOFFSPRINGAREGREYSOMEAREWHITEANDSOMEAREBLACK%XPLAIN THESEOBSERVATIONSANDDESCRIBEHOWAPOULTRYBREEDERCOULDMAKESUREHEPRODUCES all Swedish blue ducks. 3 (a) Suggest what sort of mutation causes sickle-cell disease. (b) %XPLAINWHYONEOFTHESYMPTOMSOFSICKLECELLDISEASEISSEVEREANAEMIA CW CR CW CR CW CR CW CWCW white CWCR roan CR CRCW roan CRCR red 25% white 50% roan 25% red Question D Predict how the migration patterns of normal and sickle-cell haemoglobins will differ from each other. Bull ( ) Figure 6 Genetic diagram showing probable outcome from interbreeding roan shorthorn cattle Examiner tip Always provide a key with your genetic diagrams. Indicate which symbol relates to which allele. You may be told the genotype of the female parent and of the male parent. Don’t get confused and assume that the gene in question is sex-linked. 127 178 biology.U2 M1.indd 127 3/10/08 11:02:02