Polar overdominance is a unique form of inheritance originally described in livestock, with relevant examples in humans and mice being discovered shortly after. The term polar is used to describe this type of

overdominance Overdominance is a phenomenon in genetics where the phenotype of the heterozygote lies outside the phenotypical range of both homozygous parents. Overdominance can also be described as heterozygote advantage regulated by a single genomic locus ...

because the

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

of the

heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

is more prevalent than the other

genotypes The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

. This polarity is shown as differential phenotype is only present in one of the heterozygote configurations when the recessive

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

is inherited in a parent of origin type fashion. Polar overdominance differs from regular overdominance (also known as

heterozygote advantage A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness (biology), fitness than either the homozygous Dominance (genetics), dominant or homozygous recessive gene, recessive genotype. Loci exhib ...

) where both heterozygote genotypes display a phenotype that has increased fitness regardless of the parent of origin. Studying this type of inheritance could have practical applications in preventative medicine for humans as well as a variety of other agricultural applications.

Discovery

The first described occurrence of polar overdominance in sheep was shown after finding that a

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It i ...

allele, called callipyge (after Venus Callipyge), must be inherited from the father to cause a condition called

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Although hypertro ...

. Muscle hypertrophy in the offspring is caused by an increase in the size and proportion of

muscle fibers Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, namely the fast-twitch muscle fibers. This increase is generally located in the hind quarters and torso. Muscle hypertrophy only manifests itself in the offspring approximately one month after birth.M Georges, N Cockett. The ovine callipyge locus: a paradigm illustrating the importance of non-Mendelian genetics in livestock. Reproduction, Nutrition, Development, EDP Sciences, 1996, 36 (6), pp.651-657. Polar overdominance shows evidence of an imprinted locus displayed as the difference between the expression of heterozygote phenotypes in a parent-of-origin type fashion. It was discovered that a

single-nucleotide polymorphism In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a ...

in the ''DLK1''–''DIO3'' imprinted

gene cluster A gene cluster is a group of two or more genes found within an organism's DNA that encode similar peptide, polypeptides or proteins which collectively share a generalized function and are often located within a few thousand base pairs of each othe ...

affects the gene expression of paternal allele-specific genes and several maternal allele-specific

long non-coding RNA Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as mic ...

and

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

Ectopic expression Ectopic is a word used with a prefix ecto-, meaning “out of”, and the suffix -topic, meaning "place." Ectopic expression is an abnormal gene expression in a cell type, tissue type, or developmental stage in which the gene is not usually expresse ...

of the Delta-like 1 homologue (DLK1) and the Retrotransposon-like 1 (RTL1/PEG11) genes which are paternally expressed proteins in skeletal muscle are a hallmark of these mutant individuals.

Agricultural application

More and more studies have identified quantitative trait loci (QTL) that show evidence of

genomic imprinting Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted. Partial imprinting occurs when alleles from b ...

in farm animals other than sheep. After polar overdominant inheritance was discovered to be the cause of muscular hypertrophy in sheep, the

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

for the human DLK1 gene (DLK1-GTL2

intergenic region An intergenic region is a stretch of DNA sequences located between genes. Intergenic regions may contain functional elements and junk DNA. Properties and functions Intergenic regions may contain a number of functional DNA sequences such as p ...

) was studied in pigs to try to determine the effects of inheritance on ham weight. The original purpose of this study was to find the connection between genetics and ham weight to try to produce pigs that were abnormally large compared to the average. Before conducting this research, it was also hypothesized that the locus for ham weight was related to the

ovine Sheep (: sheep) or domestic sheep (''Ovis aries'') are a domesticated, ruminant mammal typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus ''Ovis'', in everyday usage it almost always refers to dom ...

callipyge locus in sheep. After researching it was discovered that the two regions were likely unrelated due to different forms of parental inheritance exhibited in both cases and a relatively large physical distance between the loci on the chromosome. Unlike the form of paternal polar overdominance that occurs in the ovine callipyge locus, the locus that controls ham weight operates in a maternal polar overdominant fashion.

In humans

The term polar is used to describe this type of inheritance because the phenotype of one heterozygote is expressed at a level higher than other genotypes for the same locus including those displaying either homozygous geneotype. This unique form of inheritance has largely been studied in non-human mammals since 1996 until it was first described in humans in 2008. In humans, the inheritance of the alleles for the DLK1 gene (imprinted in eutherian mammals) is linked to a higher rate of obesity in the F1 generation. The imprinted DLK1-GTL2 in sheep is homologous to the DLK1 gene in humans, and includes the callipyge locus. There has been evidence to show that by screening potential fathers for a mutation at the DLK1 locus one could potentially see if their child is at a higher risk for obesity. Individuals who inherit this mutant allele from their father are more likely to show signs of obesity because the DLK1 gene is key in

adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as lipoblast ...

, or more simply the formation of fat cells.

Discovery

Agricultural application

In humans

See also

References

Further reading