Genocopy

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Genocopy is a trait that is a phenotypic copy of a genetic trait but is caused by a different genotype. [1] When a genetic mutation or genotype in one locus results in a phenotype similar to one that is known to be caused by another mutation or genotype in another locus, it is said to be a genocopy. [2] However, genocopies may also be referred to as "genetic mimics", in which the same mutation or specific genotype can result in two unique phenotypes in two different patients. [3] The term “Genocopy” was coined by Dr. H. Nachstheim in 1957, [4] in which he discusses “false” phenocopies. In comparison to when a phenotype is the result of an environmental condition that had the same effect as a previously known genetic factor such as mutation. [5] While offspring may inherit specific mutations or genotypes that result in genocopies, phenocopies are not heritable. [6] Two types of elliptocytosis that are genocopies of each other, but are distinguished by the fact that one is linked to the Rh blood group locus and the other is not. [7] The way to distinguish a recessive genocopy from a phenotype caused by a different allele would be by carrying out a test cross, breeding the two together, if they F1 hybrid segregates 1:2:1 then we can determine that it was a genocopy. [8]

Contents

Examples

Mitochondrial diseases

Since Mitochondria carry out such a variety of functions in different tissues, there are often hundreds of Mitochondrial diseases that might be harder to diagnose in early stages. Considering that there is a complex relationship between cells and genes to have metabolism at its optimum, identical Mitochondrial DNA mutations may not show up as identical diseases. Genocopies are often seen as diseases that might be caused by the same mutation but do not result in identical expression. [9] Diseases associated with mtDNA are often as a result of mutations in tRNA that play a role in Mitochondrial protein synthesis. These mutations that change protein-encoding genes or both. How each category of cause of Mitochondrial disease produces genocopies is still unknown. [10]

DiGeorge syndrome

The genocopy event between TBX1 and 22q11.2 mutations is one that shows grave symptoms. The 22q11.2 mutation leads to DiGeorge or velocardiofacial syndromes. Similarly, the mutations in the TBX1 genome exhibit the same symptoms. [11] The TBX1 haploinsufficiency is responsible for many of the traits that are also seen in 22q11.2 mutations. It has 2 mutations that are similar to the two mutations of 22q11.2 - deletion and duplication. [12] The first mutation is L411P and is a de novo mutation. [12] This mutation affects a conserved amino acid within a putative transactivation domain and is likely to affect the protein's functionality. [12] The second mutation is one that converts a cytosine to thymine in the 5’ UTR region of the TBX1 gene. This mutation increases TBX1 translational efficiency during key points in development, which is the functional equivalent to 22q11.2 duplication. [12] This shows us that genocopy is not just a discrete genomic event but can also be seen in serious diseases.

See also

Related Research Articles

An allele is one of two, or more, forms of a given gene variant. For example, the ABO blood grouping is controlled by the ABO gene, which has six common alleles. Nearly every living human's phenotype for the ABO gene is some combination of just these six alleles. An allele is one of two, or more, versions of the same gene at the same place on a chromosome. It can also refer to different sequence variations for several-hundred base-pair or more region of the genome that codes for a protein. Alleles can come in different extremes of size. At the lowest possible size an allele can be a single nucleotide polymorphism (SNP). At the higher end, it can be up to several thousand base-pairs long. Most alleles result in little or no observable change in the function of the protein the gene codes for.

Dominance (genetics) One gene variant masking the effect of another in the other copy of the gene

In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child. Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant nor recessive. Additionally, there are other forms of dominance such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.

Non-Mendelian inheritance

Non-Mendelian inheritance is any pattern of inheritance in which traits do not segregate in accordance with Mendel's laws. These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. In Mendelian inheritance, each parent contributes one of two possible alleles for a trait. If the genotypes of both parents in a genetic cross are known, Mendel's laws can be used to determine the distribution of phenotypes expected for the population of offspring. There are several situations in which the proportions of phenotypes observed in the progeny do not match the predicted values.

Pleiotropy Influence of a single gene on multiple phenotypic traits

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function.

Human genetics Study of inheritance as it occurs in human beings

Human genetics is the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling.

Genetics, a discipline of biology, is the science of heredity and variation in living organisms.

In genetics, expressivity is the degree to which a phenotype is expressed by individuals having a particular genotype. Expressivity is related to the intensity of a given phenotype; it differs from penetrance, which refers to the proportion of individuals with a particular genotype that actually express the phenotype.

Haploinsufficiency concept in genetics

Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type phenotype. Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it produces little or no gene product. Although the other, standard allele still produces the standard amount of product, the total product is insufficient to produce the standard phenotype. This heterozygous genotype may result in a non- or sub-standard, deleterious, and (or) disease phenotype. Haploinsufficiency is the standard explanation for dominant deleterious alleles.

Kearns–Sayre syndrome (KSS), Oculocraniosomatic disorder or Oculocranionsomatic neuromuscular disorder with ragged red fibers, is a mitochondrial myopathy with a typical onset before 20 years of age. KSS is a more severe syndromic variant of chronic progressive external ophthalmoplegia, a syndrome that is characterized by isolated involvement of the muscles controlling movement of the eyelid and eye. This results in ptosis and ophthalmoplegia respectively. KSS involves a combination of the already described CPEO as well as pigmentary retinopathy in both eyes and cardiac conduction abnormalities. Other symptoms may include cerebellar ataxia, proximal muscle weakness, deafness, diabetes mellitus, growth hormone deficiency, hypoparathyroidism, and other endocrinopathies. In both of these diseases, muscle involvement may begin unilaterally but always develops into a bilateral deficit, and the course is progressive. This discussion is limited specifically to the more severe and systemically involved variant.

Chromosome 22 human chromosome

Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and representing between 1.5 and 2% of the total DNA in cells.

TBX1

T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. Genes in the T-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA called T-box binding element (TBE) to control the expression of target genes.

DiGeorge syndrome Medical condition

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.

22q13 deletion syndrome Rare genetic syndrome

22q13 deletion syndrome, also known as Phelan–McDermid syndrome (PMS), is a genetic disorder caused by deletions or rearrangements on the q terminal end of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations, a definition that appears to exclude terminal deletions. The requirement to include SHANK3 in the definition is supported by many but not by those who first described 22q13 deletion syndrome.

This glossary of genetics is a list of definitions of terms and concepts commonly used in the study of genetics and related disciplines in biology, including molecular biology and evolutionary biology. It is intended as introductory material for novices; for more specific and technical detail, see the article corresponding to each term. For related terms, see Glossary of evolutionary biology.

<i>TBX5</i> (gene)

T-box transcription factor TBX5 is a protein that in humans is encoded by the TBX5 gene.

22q11.2 duplication syndrome is a rare genetic disorder caused by a duplication of a segment at the end of chromosome 22.

TANGO2

Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.

Locus heterogeneity occurs when mutations at multiple genomic loci are capable of producing the same phenotype, and each individual mutation is sufficient to cause the specific phenotype independently. Locus heterogeneity should not be confused with allelic heterogeneity, in which a single phenotype can be produced by multiple mutations, all of which are at the same locus on a chromosome. Likewise, it should not be confused with phenotypic heterogeneity, in which different phenotypes arise among organisms with identical genotypes and environmental conditions. Locus heterogeneity and allelic heterogeneity are the two components of genetic heterogeneity.

Liebenberg syndrome is a rare autosomal genetic disease that involves a deletion mutation upstream of the PITX1 gene, which is one that's responsible for the body's organization, specifically in forming lower limbs. In animal studies, when this deletion was introduced to developing birds, their wing buds were noted to take on limb-like structures.

Oligogenic inheritance describes a trait that is influenced by a few genes. Oligogenic inheritance represents an intermediate between monogenic inheritance in which a trait is determined by a single causative gene, and polygenic inheritance, in which a trait is influenced by many genes and often environmental factors.

References

  1. ↑ "Genocopy". Dictionary.com. Retrieved 30 May 2014.
  2. ↑ Jordan MA, Field J, Butzkueven H, Baxter AG (2014). "Genetic Predisposition, Humans". The Autoimmune Diseases. pp. 341–364. doi:10.1016/B978-0-12-384929-8.00026-5. ISBN   9780123849298.
  3. ↑ Sleiman PM, March M, Nguyen K, Tian L, Pellegrino R, Hou C, et al. (May 2017). "Loss-of-Function Mutations in KIF15 Underlying a Braddock-Carey Genocopy". Human Mutation. 38 (5): 507–510. doi:10.1002/humu.23188. PMID   28150392. S2CID   12398236.
  4. ↑ Nachtsheim H (February 1957). "Mutation und Phänokopie bei Säugetier und Mensch" [Mutation and phenocopy in mammals and man; their theoretical and practical importance for genetics and eugenics]. Experientia (in German). 13 (2): 57–68. doi:10.1007/BF02160092. PMID   13414769. S2CID   28201312.
  5. ↑ Baum P, Schmid R, Ittrich C, Rust W, Fundel-Clemens K, Siewert S, et al. (December 2010). "Phenocopy--a strategy to qualify chemical compounds during hit-to-lead and/or lead optimization". PLOS ONE. 5 (12): e14272. Bibcode:2010PLoSO...514272B. doi: 10.1371/journal.pone.0014272 . PMC   3000806 . PMID   21170314.
  6. ↑ Goldschmidt R (1935). "Gen und Ausseneigenschaft. I" [Gene and exterior characteristics]. Zeitschr. Ind. Abstl (in German). 69: 38–69.
  7. ↑ "Genocopy". Medical dictionary. Archived from the original on 10 June 2016. Retrieved 30 May 2014.
  8. ↑ Griffiths JF, Gelbart WM, Lewontin RC, Wessler SR, Suzuki DT, Miller JH (2005). Introduction to Genetic Analysis. New York: W.H. Freeman and Co. pp. 34–40, 473–476, 626–629. ISBN   0-7167-4939-4.
  9. ↑ "What is Mitochondrial Disease?". United Mitochondrial Disease Foundation (UMDF). 14 January 2016.
  10. ↑ Saneto RP (2017). Genetics of Mitochondrial Disease. Advances in Genetics. 98. pp. 63–116. doi:10.1016/bs.adgen.2017.06.002. ISBN   9780128122808. PMID   28942795.
  11. ↑ Kobrynski LJ, Sullivan KE (October 2007). "Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes". Lancet. 370 (9596): 1443–52. doi:10.1016/S0140-6736(07)61601-8. PMID   17950858. S2CID   32595060.
  12. 1 2 3 4 Torres-Juan L, Rosell J, Morla M, Vidal-Pou C, García-Algas F, de la Fuente MA, et al. (June 2007). "Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation". European Journal of Human Genetics. 15 (6): 658–63. doi: 10.1038/sj.ejhg.5201819 . PMID   17377518.
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