AOOAberrant crossingLossover at repeated(a)Dsequences can alsoDeletionproduceDBCArearrangements(b)PInversionDeletion(c)DuplicationH-Translocation(d)DCFig12.3
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-6 Fig 12.3 Aberrant crossing Aberrant crossingover at repeated over at repeated sequences can also sequences can also produce produce rearrangements. rearrangements
NormalRearrangedA variety of methods can15335LDDeletionD2522detect chromosomalPCRproductSmallerPCRproductrearrangements3.14.1.3'535'DABOBLDA5Inversion053'Fluorescent in situ322Yhybridization(FISH)PCRproductNoPCRproductsPCRproductprimers1+4primers1+4or2+3primers2+3PCR444.35L5ARODABDDuplication535333NoPCRproductPCRproductA43535ABCDABICH31515326Translocation55.3553EIFGHELFIGDS3362NoPCRproductsprimers2+5or4+6PCRproductPCRproductFig.12.5primers2+5primers 4+6
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-7 A variety of methods can A variety of methods can detect chromosomal detect chromosomal rearrangements rearrangements Fluorescent Fluorescent in situ hybridization (FISH) hybridization (FISH) PCR Fig. 12.5
12.2 The effects of rearrangements1. Deletions remove DNA from the genome.(a)DNAbreakagemaycausedeletionsXrays breakbothstrandsABCDEFABFGGofDNADeletionofregionCDE14-8
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-8 1. Deletions remove DNA from the genome. 1. Deletions remove DNA from the genome. 12.2 The effects of rearrangements
Deletions may have phenotypic consequencesHomozygosity for a deletion isoften,but not always,lethal.Heterozygosity for a deletionis often detrimental Evensmall deletions can be harmful.wildtype(twocopiesof Notcht)Haploinsufficiency:Half of thenormal gene dosage does notproduce enough protein productfor a normal phenotype.Vulnerability to mutation thatinactivate the remaining copy ofagene.Forexample,RB-/RB+Dell +(onecopyofNotcht)Fig.12.914-9
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-9 Deletions may have phenotypic consequences Deletions may have phenotypic consequences Fig. 12.9 Homozygosity Homozygosity for a deletion is for a deletion is often, but not always, lethal. often, but not always, lethal. Heterozygosity Heterozygosity for a deletion for a deletion is often detrimental. Even is often detrimental. Even small deletions can be harmful. small deletions can be harmful. Haploinsufficiency Haploinsufficiency: Half of the : Half of the normal gene dosage does not normal gene dosage does not produce enough protein product produce enough protein product for a normal phenotype. for a normal phenotype. Vulnerability to mutation that Vulnerability to mutation that inactivate the remaining copy of inactivate the remaining copy of a gene. For example, a gene. For example, RB /RB+
Deletions in heterozygotes can“uncover"ggenesPseudodominance-A deletion uncovers the phenotype of arecessivemutation.(a)AdeletionuncoversarecessivemutationststDelDeletedregion(b)Deletionscanbeusedtoidentifyagene'slocationGenotypeChromosomesPhenotypestst/stscarletstDeletedregionDel1st/Del1wildtypeDel2st/Del2wildtypeDel3st/Del3scarletDel4st/Del4scarletDel5st/Del5wildtypeFig. 12.614-10
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 14-10 Deletions in Deletions in heterozygotes heterozygotes can “uncover uncover” genes Pseudodominance Pseudodominance – A deletion uncovers the phenotype of a A deletion uncovers the phenotype of a recessive mutation. recessive mutation. Fig. 12.6