Null allele: Difference between revisions
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One example of a null allele is the 'O' blood type allele in the human A, B and O [[blood types|blood type system]]. The [[alleles]] for the A-[[antigen]] and B-antigen are [[Dominance relationship|co-dominant]], thus they are both [[phenotype|phenotypically]] expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single [[base pair]] change due to [[genetic mutation]]. The [[protein]] coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in [[Zygosity|homozygous]] OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele. |
One example of a null allele is the 'O' blood type allele in the human A, B and O [[blood types|blood type system]]. The [[alleles]] for the A-[[antigen]] and B-antigen are [[Dominance relationship|co-dominant]], thus they are both [[phenotype|phenotypically]] expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single [[base pair]] change due to [[genetic mutation]]. The [[protein]] coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in [[Zygosity|homozygous]] OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele. |
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Null alleles can have lethal effects. Mice homozygous for a null allele for insulin die 48 - 72 hours after birth.<ref>{{cite journal|last1=Accili|first1=Domenico|last2=Drago|first2=John|last3=Lee|first3=Eric|last4=Johnson|first4=Mark|last5=Cool|first5=Martha|last6=Salvatore|first6=Paola|last7=Asico|first7=Laureano|last8=Jose|first8=Pedro|last9=Taylor|first9=Simeon|last10=Westphal|first10=Heiner|title=Early neonatal death in mice homozygous for a null allele of the insulin receptor gene|journal=Nature Genetics|date=January 12, 1996|volume=12|page=106|accessdate=26 May 2017}}</ref> |
Null alleles can have lethal effects. Mice homozygous for a null allele for insulin die 48 - 72 hours after birth.<ref>{{cite journal|last1=Accili|first1=Domenico|last2=Drago|first2=John|last3=Lee|first3=Eric|last4=Johnson|first4=Mark|last5=Cool|first5=Martha|last6=Salvatore|first6=Paola|last7=Asico|first7=Laureano|last8=Jose|first8=Pedro|last9=Taylor|first9=Simeon|last10=Westphal|first10=Heiner|title=Early neonatal death in mice homozygous for a null allele of the insulin receptor gene|journal=Nature Genetics|date=January 12, 1996|volume=12|page=106|accessdate=26 May 2017}}</ref> |
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== Evidence == |
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==== Polymerase Chain Reaction (PCR) ==== |
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A microsatellite null allele is an allele at a [[microsatellite]] locus that does not amplify to detectable levels in a [[polymerase chain reaction]] test.<ref name=":0">{{Cite journal|last=Dakin|first=E E|last2=Avise|first2=J C|date=2004-08-04|title=Microsatellite null alleles in parentage analysis|url=https://www.nature.com/articles/6800545|journal=Heredity|language=en|volume=93|issue=5|pages=504–509|doi=10.1038/sj.hdy.6800545|issn=1365-2540}}</ref> Microsatellite regions are usually characterized by repeated sequences of nucleotides.<ref name=":0" /> Primers that are specific to a particular locus are used in PCR amplification to bind to these nucleotide sequence repeats and, thus, identify a microsatellite.<ref name=":1">{{Cite journal|last=Primmer|first=C. R.|last2=Møller|first2=A. P.|last3=Ellegren|first3=H.|date=August 1995|title=Resolving genetic relationships with microsatellite markers: a parentage testing system for the swallow Hirundo rustica|url=https://www.ncbi.nlm.nih.gov/pubmed/8574445?dopt=Abstract&holding=npg|journal=Molecular Ecology|volume=4|issue=4|pages=493–498|issn=0962-1083|pmid=8574445}}</ref><ref name=":0" /> The primers anneal to reference sequences derived from source organisms in a genomic library. Divergence from the reference sequences (from genetic mutations) results in poor annealing of the primers and lower amplification in a PCR experiment.<ref name=":1" /> |
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==== Parentage Analysis ==== |
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Strong evidence of null alleles was first seen in analysis of bears in 1995.<ref name=":2">{{Cite journal|last=Paetkau|first=D.|last2=Strobeck|first2=C.|date=1995-08-01|title=The molecular basis and evolutionary history of a microsatellite null allele in bears|url=http://onlinelibrary.wiley.com/doi/10.1111/j.1365-294X.1995.tb00248.x/abstract|journal=Molecular Ecology|language=en|volume=4|issue=4|pages=519–520|doi=10.1111/j.1365-294x.1995.tb00248.x|issn=1365-294X}}</ref> In this analysis, a known parent was determined to be homozygous at a certain locus, but produced offspring that expressed a different "homozygous" genotype.<ref>{{Cite journal|last=Dakin|first=E E|last2=Avise|first2=J C|date=2004-08-04|title=Microsatellite null alleles in parentage analysis|url=https://www.nature.com/articles/6800545|journal=Heredity|language=en|volume=93|issue=5|pages=504–509|doi=10.1038/sj.hdy.6800545|issn=1365-2540}}</ref> This result led to the inference that the parent and offspring were both heterozygous for the locus being studied.<ref name=":2" /> |
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==See also== |
==See also== |
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Revision as of 07:44, 10 November 2017
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A null allele is a nonfunctional copy of a gene caused by a genetic mutation. This mutation can cause complete lack of production of the associated gene product or a product that does not function properly. A null allele cannot be distinguished from deletion of the entire locus solely from phenotypic observation.[1]
A mutant allele that produces no protein is called a protein null (shown by western analysis), and one that produces no RNA is called an RNA null (shown by Northern analysis or by DNA sequencing of a deletion allele). A genetic null or amorphic allele has the same phenotype when homozygous as when heterozygous with a deficiency that disrupts the locus in question. A genetic null allele can be a protein and RNA null, but can also express normal levels of a gene product that is non-functional due to mutation.
Another definition of null allele concerning molecular markers, refers to such a marker in the case it can no longer be detected because of a mutation. For example, microsatellites (i.e. a repetitive sequence of DNA, in which the repeat is rather short) are used as molecular markers amplifying them through PCR. To do so, a primer or oligonucleotide aligns with either of ends of the locus. If a mutation occurs in the annealing site, then the marker can no longer be used and the allele is turned into a null allele.
One example of a null allele is the 'O' blood type allele in the human A, B and O blood type system. The alleles for the A-antigen and B-antigen are co-dominant, thus they are both phenotypically expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single base pair change due to genetic mutation. The protein coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in homozygous OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele.
Null alleles can have lethal effects. Mice homozygous for a null allele for insulin die 48 - 72 hours after birth.[2]
Evidence
Polymerase Chain Reaction (PCR)
A microsatellite null allele is an allele at a microsatellite locus that does not amplify to detectable levels in a polymerase chain reaction test.[3] Microsatellite regions are usually characterized by repeated sequences of nucleotides.[3] Primers that are specific to a particular locus are used in PCR amplification to bind to these nucleotide sequence repeats and, thus, identify a microsatellite.[4][3] The primers anneal to reference sequences derived from source organisms in a genomic library. Divergence from the reference sequences (from genetic mutations) results in poor annealing of the primers and lower amplification in a PCR experiment.[4]
Parentage Analysis
Strong evidence of null alleles was first seen in analysis of bears in 1995.[5] In this analysis, a known parent was determined to be homozygous at a certain locus, but produced offspring that expressed a different "homozygous" genotype.[6] This result led to the inference that the parent and offspring were both heterozygous for the locus being studied.[5]
See also
References
- ^ Peter., Snustad, D. (2012). Genetics. Simmons, Michael J. (6th ed., International student version ed.). Singapore: Wiley. ISBN 1118092422. OCLC 770517281.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ Accili, Domenico; Drago, John; Lee, Eric; Johnson, Mark; Cool, Martha; Salvatore, Paola; Asico, Laureano; Jose, Pedro; Taylor, Simeon; Westphal, Heiner (January 12, 1996). "Early neonatal death in mice homozygous for a null allele of the insulin receptor gene". Nature Genetics. 12: 106.
{{cite journal}}:|access-date=requires|url=(help) - ^ a b c Dakin, E E; Avise, J C (2004-08-04). "Microsatellite null alleles in parentage analysis". Heredity. 93 (5): 504–509. doi:10.1038/sj.hdy.6800545. ISSN 1365-2540.
- ^ a b Primmer, C. R.; Møller, A. P.; Ellegren, H. (August 1995). "Resolving genetic relationships with microsatellite markers: a parentage testing system for the swallow Hirundo rustica". Molecular Ecology. 4 (4): 493–498. ISSN 0962-1083. PMID 8574445.
- ^ a b Paetkau, D.; Strobeck, C. (1995-08-01). "The molecular basis and evolutionary history of a microsatellite null allele in bears". Molecular Ecology. 4 (4): 519–520. doi:10.1111/j.1365-294x.1995.tb00248.x. ISSN 1365-294X.
- ^ Dakin, E E; Avise, J C (2004-08-04). "Microsatellite null alleles in parentage analysis". Heredity. 93 (5): 504–509. doi:10.1038/sj.hdy.6800545. ISSN 1365-2540.