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sequencelengths 384
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to\tcut\tthe\tDNA.\tCas9\tis\tmost\toften\tused,\tbut\tother\tenzymes\tcan\talso\tbe\tcombined\twith\tCRISPR\nsuch\tas\tCas11\tand\tCpf1.\tThe\tcell’s\tDNA\trepair\tmechanism\tthen\trepairs\tthe\tbreak,\tintroducing\nchanges\talso\tencoded\n\ton\tthe\tguide\tRNA.\nSince\tCRISPR\tis\tmuch\tmore\taccurate\tand\tefficient\tthan\tprevious\tgenome\tediting\ttechnologies, | [
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researchers\tare\texploring\tthe\tpossibility\tof\tusing\tit\tto\tcorrect\tgenetic\tdiseases\tin\thumans.\tSingle-\ngene\tdisorders\tsuch\tas\tsickle\tcell\tanemia,\tcystic\tfibrosis,\tand\tother\tmendelian\tdisorders\tare\tlikely\nfirst\tcandidates\tfor\tthis\ttreatment.\tHowever,\treports\tof\tchanges\tin\tnontargeted\tparts\n\tof\tthe | [
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technology\tto\tcomplex\tdiseases\tand\tthe\tline\tbetween\tfighting\tdisease\tand\tunnecessary\nenhancement\talso\n\tremain\tprovocative\ttopics.\nThe\ttechnology\talso\topens\tdebate\tabout\tresponsible\tways\tto\tedit\thuman\tgenomes.\tEditing\ta\nperson’s\town\tcells,\tknown\tas\tsomatic\tediting,\taffects\tonly\tthe\tindividual;\tediting\tgermline\tcells | [
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technology.\nThe\trate\tof\tprogress\tof\tapplying\tgenomics\tin\tclinical\tapplications\tis\tassociated\tstrongly\twith\nprogress\tin\tidentifying\tassociations\tbetween\tdiseases\tand\t\nsingle\tnucleotide\tpolymorphisms\n(SNPs,\tpronounced\t“snips”).\tOnce\ta\tstrong\tassociation\thas\tbeen\tdetermined,\tdiagnostic\ttests\tand\nappropriate | [
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this\tgenetic\tvariation\tsuggests,\tthe\tchange\tinvolves\ta\tsingle\tnucleotide.\tThe\tinitial\tmolecular\napproach\tto\tassociating\tmutations\twith\tsusceptibility\tto\tdisease\twas\tto\tlook\tfor\tSNPs\t(changes)\tin\ngenes\tthat\tencoded\timportant\tmetabolic\tproteins.\tThis\tapproach\thas\tbeen\tsomewhat\tsuccessful\tbut\nnot\tsufficiently | [
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not\tsufficiently\n\tsuccessful\tin\tunderstanding\tthe\tgenetic\tand\tenvironmental\tcomplexity\tof\tchronic\ndisorders.\tAs\ta\tresult,\tmore\trecently\tthe\tspeed\tof\twhole\tgenome\tsequencing\thas\tincreased\nsubstantially\tand\tthe\tcost\thas\tdecreased,\twhich\thave\tallowed\ta\tshift\tto\t\ngenome-wide\tassociation\nstudies\t(GWAS) | [
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genome-wide\tassociation\nstudies\t(GWAS)\n\tas\tthe\tpreferred\tgenomic\ttool\tfor\tdetecting\tSNPs.\tGWAS\tallows\tthe\tdetection\tof\npatterns\tof\tmultiple\tSNPs\tassociated\n\twith\ta\tdisease\tand\tis\tparticularly\tuseful\tfor\tcomplex\tdisorders.\nSee\t\nBox\t6.11\n\tfor\tadditional\tinformation.\nBOX\t6.11\nDetecting\tGene\tVariants:\tCandidate\tGene\tvs.\tGWAS | [
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(GWAS).\tThe\t\ncandidate\tgene\tapproach\n\twas\tthe\toriginal\ttool.\tIt\tfocuses\ton\tfunctional\tvariants\nand\tpositional\tvariants.\tFunctional\tvariants\tresult\tfrom\n\tmutations\tin\tgenes\twhose\tproducts\tare\nknown\tto\tbe\tinvolved\tin\tthe\tmechanisms\tunderlying\tthe\tdisease\tof\tinterest.\tThe\tpositional | [
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mechanisms\nhave\tnot\tbeen\tthoroughly\tdefined,\tit\tis\tlikely\tthat\tnovel\tgenes\twill\tnot\tbe\tdetected.\tFurther,\ta\nlarge\tcohort\tis\toften\tneeded\tin\torder\tto\tinclude\tsufficient\tsubjects\thomozygous\tfor\tthe\trisk\tallele.\nCandidate\tgenes\thave\tbeen\tmost\tsuccessful\tfor\tsingle\tgene\tdisorders. | [
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Candidate\tgenes\thave\tbeen\tmost\tsuccessful\tfor\tsingle\tgene\tdisorders.\nLifestyle-related\tchronic\tdiseases,\thowever,\ttend\tto\tbe\tcomplex\ttraits\tand\tthe\tcomplexity\tis\nfurther\tcompounded\tby\tthe\n\tepigenetic\tcomponent.\tDevelopment\tof\tthese\tdiseases\ttypically\nrequires\tthe\tinteraction\tof\ta\tgenetic\tsusceptibility\tcreated\tby\ta\tgene\tvariant\twith\tenvironmental | [
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factors.\tThese\tfactors\tare\ttypically\tmodifiable\tand\tinvolve\tlifestyle\tchoices\tsuch\tas\tthe\tfood\twe\neat,\twhether\twe\texercise\tregularly,\thow\twell\twe\tmanage\tour\tthoughts\tand\temotions,\tthe\tquality\nof\trelationships\tand\tsystems\tof\tmeaning,\tthe\tquality\n\tand\tquantity\tof\tour\tsleep,\tand\tour\texposure | [
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but\tparticularly\tby\tthe\tGWAS\tapproach,\tgreatly\tbenefits\tfrom\tthe\tdevelopment\tof\tbioinformatics\nand\tits\thigh-capacity\tcomputer\torganization\tand\tanalysis.\nIn\taddition\tto\tSNPs,\tother\ttypes\tof\tvariations\talso\tmay\tplay\tan\timportant\trole\tin\tthe\tgenotypic\tand\nphenotypic\tvariation\tamong\thumans.\tLoss\tor\tgain\tof\tmore\n\tthan\tone\tnucleotide\t(deletions\tand | [
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which\thave\tnutritional\timplications\tsuch\tas\tassistance\twith\tfeeding.\tDescriptions\tof\tthe\tchanges\tand\ntheir\tconsequences\tcan\tbe\tfound\tin\tclinical\n\tgenetics\ttextbooks\tas\twell\tas\tonline\tin\tresources\tsuch\tas\nthe\tGenetic\tand\tRare\tDiseases\tInformation\tCenter\tand\tthe\tMendelian\tInheritance\tin\tMan\ncompendium. | [
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compendium.\nAn\texample\tof\ta\tnonfatal\tchromosomal\tabnormality\tis\ttrisomy\t21\t(Down’s\tsyndrome).\tTypically\nseen\tis\tan\textra\tcopy\tof\tthe\twhole\tchromosome\tresulting\tfrom\tan\terror\tin\tdistributing\tthe\nchromosomes\tduring\tsperm\tor\tegg\tformation.\tHowever,\tthe\tcharacteristics\n\tof\tDown’s\tsyndrome\tare | [
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weight,\tdiabetes,\tand\tcardiovascular\tcomplications.\nVarying\tdegrees\tof\tmental\tinsufficiency\toften\tcomplicate\ttherapy.\tNutrition\tprofessionals\tcan\thelp\nmitigate\tthe\tdetrimental\teffects\tof\tthese\tdisorders\ton\tnutritional\tstatus\t(see\t\nChapter\t43\n).\nDisease\tat\tthe\tmitochondrial\tlevel | [
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0.08665157854557037,
-0.03375493362545967
] |
Chapter\t43\n).\nDisease\tat\tthe\tmitochondrial\tlevel\nDue\tto\tthe\tmajor\trole\tthat\tmitochondria\tplay\tin\tenergy\tproduction,\talterations\tin\tmtDNA\tare\nfrequently\tdegenerative\n\tand\thave\tvaried\tclinical\tmanifestations\tbecause\tof\tthe\tmultiple\tcopies\tof\nmtDNA,\tnot\tall\tof\twhich\tmay\tcontain\tthe\tgenetic\tchange.\tMutations\tin\tmtDNA\tcan\tmanifest\tat\tany | [
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] |
age\tand\tinclude\tneurologic\tdiseases,\tcardiomyopathies,\tand\tskeletal\tmyopathies.\tAn\tincreasing\nnumber\tof\tdiseases\tare\tbeing\tlinked\tto\tmutations\tin\tmtDNA.\tOne\tof\tthe\tearliest\tdisorders\tto\tbe\ntraced\tto\tmtDNA\tis\tWolfram’s\tsyndrome,\ta\n\tform\tof\tdiabetes\twith\tassociated\tdeafness.\tSubsequently, | [
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form\tof\tdiabetes\twith\tassociated\tdeafness.\tSubsequently,\ngene\tvariants\thave\tbeen\tfound\tthat\trelate\tto\teach\tof\tthe\tcomponents\tof\tthe\toxidative\nphosphorylation\tpathway.\tThe\tphysiologic\tconsequences\tof\tthese\tmutations\ttypically\tinvolve\torgans\nthat\thave\ta\thigh\tdemand\tfor\tenergy,\tsuch\tas\tthe\theart,\tkidneys,\tbrain,\tand\tmuscles.\tSee\tthe\tNational | [
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Institutes\tof\tHealth\tGenetics\tHome\tReference\twebsite\tfor\tinformation\n\ton\tmtDNA-based\tdisorders\nand\tMITOMAP,\ta\thuman\tmitochondrial\tgenome\tdatabase,\tfor\tspecifics\ton\thuman\tmtDNA\tvariants.\nDisease\tat\tthe\tmolecular\tlevel\nThe\tmajority\tof\tdisease\tconditions\tassociated\twith\tgenomics\tinvolve\tchanges\tat\tthe\tmolecular\tlevel. | [
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may\tresult\tin\tdevelopmental\tdisabilities,\toral-motor\tproblems,\tsusceptibility\tto\n\tweight\tgain,\tand\ndifficulties\twith\tconstipation.\tExamples\tinclude\tAlbright\thereditary\tosteodystrophy,\twhich\tcommonly\nresults\tin\tdental\tproblems,\tobesity,\thypocalcemia,\tand\thyperphosphatemia;\tchondrodysplasias,\twhich | [
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often\tresult\tin\toral-motor\tproblems\tand\tobesity;\tand\tMarfan\tsyndrome,\twhich\tinvolves\tcardiac\ndisease,\texcessive\tgrowth,\tand\tincreased\tnutritional\tneeds.\tFamilial\thypercholesterolemia\t(type\n\t2\nfamilial\tdyslipidemia)\tresults\tfrom\ta\tdefective\tlow-density\tlipoprotein\treceptor\t(\nLDLR\n\tgene), | [
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LDLR\n\tgene),\ntransmitted\tas\tan\tautosomal\tdominant\ttrait.\tSymptoms\tinclude\televated\tlevels\tof\ttotal\tcholesterol,\nelevated\tlevels\tof\tLDL\tcholesterol,\tand\tincreased\trisk\tof\tatherosclerosis.\nAutosomal\trecessive\tdisorders\tare\tmore\tcommon.\tThey\twere\ttraditionally\tdetected\tbecause\tthe\nmutation\thad\ta\tdetrimental\teffect | [
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HBB\n\tgene.\tMetabolic\tdisorders\tof\tamino\tacid,\tcarbohydrate,\nand\tlipid\tmetabolism,\tdesignated\tas\tinborn\terrors\tof\tmetabolism\t(IEM),\tare\tsimilarly\theritable\tand\nassociated\twith\ta\tparticular\tmutation.\tIEM\tdisorders\n\tare\tthe\tearliest\tknown\texamples\tof\tnutritional\ngenomics,\tand\tdietary\tmodification\tremains\tthe\tprimary\ttreatment\t(see\t\nChapter\t42 | [
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] |
Chapter\t42\n).\tA\tbrief\noverview\tof\tIEM\tfrom\ta\tgenetic\tperspective\tis\tincluded\there\tto\temphasize\tthe\timportant\trole\tof\tthe\nnutrition\tprofessional\tin\trestoring\thealth\tto\tthese\tindividuals\tand\tto\tcontrast\tIEM\twith\tchronic\ndisorders,\twhich\tresult\tfrom\tthe\tsame\ttype\tof\tgenetic\tchange\tbut\n\taffect\tfunction\tless\tseverely.\tA | [
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ALDOB\n\tgene\tencoding\taldolase\tB\t(fructose-1,6-\nbiphosphate\taldolase)\timpairs\tthe\tcatalytic\tactivity\tof\tthe\tenzyme\tand\tprevents\tfructose\tfrom\tbeing\nconverted\tto\tglucose.\tBreast-fed\tinfants\tare\ttypically\tasymptomatic\tuntil\tfruit\tis\tadded\tto\n\tthe\tdiet.\nNutrition\ttherapy\tinvolves\tthe\telimination\tof\tfructose,\tsorbitol,\tand\tthe\tfructose-containing | [
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genotype\n)\tis\tpermanent,\tthe\t\nphenotype\n\tis\tnot.\nIn\tspite\tof\tan\tindividual\thaving\tmutations\tthat\tpredispose\tto\tdisease,\teliminating\tspecific\tfoods\tand\nfood\tingredients\tessentially\tkeeps\n\tthe\tdisease\tsusceptibility\tsilent,\tand\tthe\tinfant\twill\tenjoy\tnormal\ndevelopment.\tNutrition\tprofessionals\tare\tinvaluable\tfor\tbeing\table\tto\tdetect\tthe\tproblem\tand | [
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and\textreme\tmuscle\twasting.\tChildren\ttypically\tare\tconfined\tto\ta\twheelchair\tby\tthe\ttime\tthey\treach\ntheir\tteens\tand\tneed\tassistance\twith\tfeeding.\nY-linked\tinheritance\tdisorders\tprimarily\tinvolve\tmale\tsex\tdetermination.\tAt\tthis\ttime\tno\tnutrition-\nrelated\tdisorders\thave\tbeen\tassigned\tconclusively\n\tto\tthe\tY\tchromosome. | [
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] |
to\tthe\tY\tchromosome.\nIn\tsummary,\tany\tgene\tpotentially\tcan\tundergo\tmutation,\twhich\tcan\taffect\tthe\tfunction\tof\tits\nprotein\tand\tthe\thealth\tof\tthe\tindividual.\tIts\tlocation\twithin\tthe\tnuclear\tDNA\tor\tmtDNA\tdetermines\tits\nmode\tof\tinheritance.\tSee\t\nChapter\t42\n\tfor\tmore\tinformation\tabout\tgenetic\tand\tmetabolic\tdisorders.\nDisease\tat\tthe\tepigenetic\tlevel | [
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environmental\ttriggers.\tDetails\tmust\tawait\tthe\toutcomes\tof\tthe\tmany\tstudies\tcurrently\tunderway.\nInstead,\tlet’s\ttake\ta\tmoment\tto\tacknowledge\tthe\tvaluable\tcontributions\tof\tnutrition\n\tpioneers\twho\nalerted\tthe\tfield\tto\tthe\timportance\tof\tnutrition-related\tepigenetics\tto\thealth.\tOrnish\tdemonstrated | [
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metabolic,\tand\tphysiologic\tlevels.\nNutritional\tgenomics\tand\tchronic\tdisease\nHealth\tcare\tproviders\tare\tgradually\tincorporating\tthe\tvarious\t“omic”\tdisciplines\tinto\tassessment,\ndiagnosis,\n\tintervention,\tand\tmonitoring/evaluation.\tTo\tdo\tso\trequires\ta\tdeep\tfoundation\tof | [
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developed,\ttested,\tand\tapplied.\nIn\tcontrast,\tthe\tmajority\tof\tclinic\tvisits\tare\tfor\tpatients\twith\tone\tor\tmore\tcomplex\tchronic\n\tdiseases.\nRestoring\thealth\tor\tpreventing\tdisease\tin\tthe\tcase\tof\tchronic\tdisorders\tis\tan\tambitious\tundertaking\nthat\twill\tlikely\trequire\tdecades\tof\tbasic\tand\tclinical\tresearch\tbefore\tthe\tpotential\tis\tfully\trealized. | [
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Nutritional\tgenomics\n\tis\ta\tfield\tof\tstudy\tfocused\ton\nthe\tinteraction\tbetween\tgenes,\tdiet,\tlifestyle\tfactors,\tand\thuman\thealth.\tIncluded\twithin\tnutritional\ngenomics\tare\t\nnutrigenetics\n,\n\t\nnutrigenomics\n,\tand\tnutrition-related\taspects\tof\t\nepigenetics\n\tand\nepigenomics\n,\twhich\tprovide\tinsight\n\tinto\thow\tenvironmental\tfactors\tregulate\tgene\texpression. | [
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into\thow\tenvironmental\tfactors\tregulate\tgene\texpression.\nNutritional\tgenomics\tand\tits\tsubdisciplines\tencompass\tnumerous\tother\tdisciplines:\tmolecular\nbiology,\tbiochemistry,\tintermediary\tmetabolism,\ttranscriptomics,\tproteomics,\tmetabolomics,\tthe\nmicrobiome,\tneuroscience,\tand\tbehavioral\tchange.\tSee\tthe\tAcademy\tof\tNutrition\tand\tDietetics | [
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review\ton\tnutritional\tgenomics\tfor\tan\toverview\tof\tcurrent\tprogress\n\tin\tthe\tfield\t(\nRozga\tand\tHandu,\n2018\n).\tAs\tthese\tdisciplines\tevolve,\tpractitioners\twill\tincreasingly\tbe\table\tto\ttailor\tdiet\tand\tlifestyle\nchoices\tto\tthe\tgenetic\tmakeup\tof\teach\tclient.\nNutrigenetics\tconcerns\tthe\teffect\tof\tgenetic\tvariation\ton\tthe\tresponse\tto\tnutrients\tand\tother | [
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dietary\tinput.\tFor\texample,\tan\toften-cited\tillustration\tof\tnutrigenetics\tinvolves\ta\tvariant\tin\tthe\t5,10-\nmethylenetetrahydrofolate\n\treductase\t(\nMTHFR\n)\tgene.\tMutations\tin\tthis\tgene\tcan\tresult\tin\ta\nsubstantial\tdecrease\tin\tenzyme\tactivity\twhich\tis\tresponsible\tfor\tconverting\tdietary\tfolate\tor\tfolic\tacid | [
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translate\tthis\tinformation\tinto\tdiet-and-lifestyle\tapproaches\tpersonalized\tto\tthe\tindividual.\n\tIn\tthe\nshorter\tterm,\tthe\texpectation\tis\tthat\tthe\tinformation\tcan\tbe\tused\tto\tmove\taway\tfrom\tone-size-fits-all\nto\tidentifying\tcategories\tof\tindividuals\twith\tchronic\tdisease\twho\twould\tbenefit\tfrom\ta\tsimilar | [
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being\tconducted\tin\tan\tappropriately\n\tcredentialed\tlaboratory\t(at\tleast\tCLIA-certified)?\n•\t\nHow\twill\tthe\tclient’s\tprivacy\tbe\tprotected?\n•\t\nWhat\tis\tthe\tcost\tof\tthe\ttest?\n•\t\nTo\twhom\twill\tthe\ttest\tresults\tbe\tsent?\n•\t\nHow\tlong\tbefore\tthe\tresults\twill\tbe\tavailable?\n• | [
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•\t\nHow\tlong\tbefore\tthe\tresults\twill\tbe\tavailable?\n•\t\nIs\tthe\tDNA\tsample\tdestroyed\tfollowing\tanalysis?\tIf\tsaved,\thow\twill\tit\tbe\tused\tin\tthe\tfuture?\nThe\tconsumer\twill\tneed\tto\tprovide\twritten\tconsent\tto\thave\ttheir\tsample\tretained\n\tand\tused\nfor\tfuture\tanalyses.\n•\t\nWhat\twill\tbe\tincluded\tin\tthe\treport\tof\tthe\ttest\tresults?\n• | [
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•\t\nWhat\twill\tbe\tincluded\tin\tthe\treport\tof\tthe\ttest\tresults?\n•\t\nWhich\tvariants\twill\tbe\texamined\tand\tare\trs\tnumbers\treported\talong\twith\tthe\tSNP?\n•\t\nWhat\tis\tthe\tassociation\tof\teach\tvariant\twith\ta\tdisease?\tDoes\tthe\tcompany\tmake\tthe\tstudies\navailable\tthat\tlink\tthe\tvariants\t(SNPs)\twith\tdiseases?\n• | [
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available\tthat\tlink\tthe\tvariants\t(SNPs)\twith\tdiseases?\n•\t\nWhich\tlifestyle\tchoices\tare\tparticularly\timportant\tin\tpromoting\tdisease\n\twhen\tthis\tvariant\tis\npresent?\nSeveral\tprominent\tnutritional\tgenomics\tresearchers\thave\tproposed\tguidelines\tfor\tevaluating\tthe\nvalidity\tof\tnutrigenetic\ttesting\tand\tits\tuse\tfor\tdietary\tadvice\t(\nGrimaldi\tet\tal,\t2017 | [
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Grimaldi\tet\tal,\t2017\n).\tAdditionally,\tthe\nAcademy\tof\tNutrition\tand\tDietetics’\t2014\tnutritional\tgenomics\tposition\tpaper\tdescribes\tthe\tvarious\ngovernmental\tagencies\tthat\thave\tat\tleast\tsome\toversight\tof\tnutritional\n\tgenomics,\tparticularly\tdirect-\nto-consumer\ttesting\t(\nCamp\tand\tTrujillo,\t2014\n). | [
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to-consumer\ttesting\t(\nCamp\tand\tTrujillo,\t2014\n).\nThe\tinformation\tthat\tis\tgenerated\tby\tgenetic\ttests\tcan\tprovide\tinsight\tinto\tan\tindividual’s\tpresent\nhealth\tstatus\tand\tfuture\tdisease\tsusceptibilities\tto\ta\tmuch\tgreater\tdegree\tthan\thas\tbeen\tpossible\tto | [
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date.\tClients\twill\twant\tto\tknow\tthat\ttheir\tinformation\twill\tbe\theld\tprivate\tlike\tany\tother\thealth\tcare\ndata\tand\tthat\n\tit\tcannot\tbe\tused\tto\tdiscriminate\tagainst\tthem\tin\tobtaining\temployment\tor\tinsurance.\nUnintended\tconsequences\tof\tgenetic\ttesting\tare\toften\tcauses\tof\tconcern\tfor\tclients,\tand\tthe\tincrease | [
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in\tgenetic\ttesting\tacross\thealth\tcare\tmakes\tunderstanding\tthose\tconsequences\tespecially\timportant\nfor\tnutrition\tprofessionals.\tSee\t\nBox\t6.13\n\tfor\tmore\ton\tthis\ttopic.\nBOX\t6.13\nELSI:\tEthical,\tLegal,\tand\tSocial\tImplications\n\t\nof\tGenomics\nFor\tthe\tvarious\t“omic”\ttechnologies\tto\tbe\thelpful\tin\tthe\tclinic,\tclients\tmust\tbe\tcomfortable\twith | [
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their\tuse.\tOf\tparticular\tconcern\tto\tclients\thas\tbeen\twhether\tgenetic\tinformation\tin\tthe\thands\tof\ninsurers\tor\temployers\tcould\tlead\tto\tdiscrimination\tagainst\tapplicants.\tThese\tand\tother\tissues\tare\nthe\tsubject\tof\tdebate\tand\tresearch\tinto\tthe\tethical,\tlegal,\tand\tsocial\timplications\t(ELSI)\n\tof\tgenetic\nresearch\tand\ttechnologies. | [
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firing,\tpromotion,\tor\tjob\tplacement\tdecisions\tbased\ton\tgenetic\tinformation.\nHowever,\tas\tthe\tpopularity\tof\tdirect-to-consumer\tgenetic\ttesting\thas\tincreased,\tthe\tissue\tof\nprivacy\tand\tnondiscrimination\tcontinues\tto\tbe\tof\tconcern\tto\tconsumers\n\tand\tto\tvarious\ngovernmental\tagencies.\tThe\tFederal\tTrade\tCommission\thas\tbegun\ttaking\ta\tcareful\tlook\tat\thow | [
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