Non-Mendelian inheritance

Non-Mendelian inheritance
Non-Mendelian inheritance is a general term that refers to 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.
Although inheritance of traits in fungi, viruses, and bacteria are all non-Mendelian, the
phrase "non-Mendelian inheritance" is usually only used to describe the exceptions which
occur in eukaryotic reproduction.
Non-Mendelian inheritance plays a role in several disease processes
Extranuclear inheritance
Extranuclear inheritance (also known as cytoplasmic inheritance) is a form of nonMendelian inheritance first discovered by Carl Correns in 1908.[4] While working with
Mirabilis jalapa Correns observed that leaf color was dependent only on the genotype of
the maternal parent. Based on this data, he determined that the trait was transmitted
through a character present in the cytoplasm of the ovule. Later research by Ruth Sager
and others identified DNA present in chloroplasts as being responsible for the unusual
inheritance pattern observed. Work on the poky strain of the mold Neurospora crassa
begun by Mary and Hershel Mitchell[5] ultimately led to the discovery of genetic
material in mitochondria as well.
According to the endosymbiont theory, mitochondria and chloroplasts were once free
living organisms that were taken up by a eukaryotic cell.[6] Over time, mitochondria and
chloroplasts formed a symbiotic relationship with their eukaryotic hosts. Although the
transfer of a number of genes from these organelles to the nucleus prevents them from
living independently, each still possesses genetic material in the form of double stranded
It is the transmission of this organellar DNA that is responsible for the phenomenon of
extranuclear inheritance. Both chloroplasts and mitochondria are present in the cytoplasm
of maternal gametes only. Thus, the phenotype of traits linked to genes found in either
chloroplasts or mitochondria are determined exclusively by the maternal parent.
In humans, mitochondrial diseases are a class of diseases, many of which affect the
muscles and the eye.
Gene conversion
Gene conversion can be one of major forms of non-Mendelian inheritance. Gene
conversion is a reparation process in DNA recombination, by which a piece of DNA
sequence information is transferred from one DNA helix (which remains unchanged) to
another DNA helix, whose sequence is altered. This may occur as a mismatch repair
between the strands of DNA which are derived from different parents. Thus the mismatch
repair can convert one allele into the other. This phenomenon can be detected through the
offspring non-Mendelian ratios, and is frequently observed, e.g., in fungal crosses.[7]
Infectious heredity
Another form of non-Mendelian inheritance is known as infectious heredity. Infectious
particles such as viruses may infect host cells and continue to reside in the cytoplasm of
these cells. If the presence of these particles results in an altered phenotype, then this
phenotype may be subsequently transmitted to progeny.[8] Because this phenotype is
dependent only on the presence of the invader in the host cell’s cytoplasm, inheritance
will be determined only by the infected status of the maternal parent. This will result in a
uniparental transmission of the trait, just as in extranuclear inheritance.
One of the most well studied examples of infectious heredity is the killer phenomenon
exhibited in yeast. Two double-stranded RNA viruses, designated L and M, are
responsible for this phenotype.[9] The L virus codes for the capsid proteins of both
viruses, as well as an RNA polymerase. Thus the M virus can only infect cells already
harboring L virus particles. The M viral RNA encodes a toxin which is secreted from the
host cell. It kills susceptible cells growing in close proximity to the host. The M viral
RNA also renders the host cell immune to the lethal effects of the toxin. For a cell to be
susceptible it must therefore be either uninfected, or harbor only the L virus.
The L and M viruses are not capable of exiting their host cell through conventional
means. They can only transfer from cell to cell when their host undergoes mating. All
progeny of a mating involving a doubly infected yeast cell will also be infected with the
L and M viruses. Therefore, the killer phenotype will be passed down to all progeny.
Heritable traits that result from infection with foreign particles have also been identified
in Drosophila. Wild type flies normally full recover after being anesthetized with carbon
dioxide. Certain lines of flies have been identified that die off after exposure to the
compound. This carbon dioxide sensitivity is passed down from mothers to their progeny.
This sensitivity is due to infection with Sigma virus, a rhabdovirus only capable of
infecting Drosophila
Although this process is usually associated with viruses, recent research has shown that
the Wolbachia bacterium is also capable of inserting its genome into that of its host.[
Genomic imprinting
Genomic imprinting represents yet another example of non-Mendelian inheritance. Just
as in conventional inheritance, genes for a given trait are passed down to progeny from
both parents. However, these genes are epigenetically marked before transmission,
altering their levels of expression. These imprints are created before gamete formation
and are erased during the creation of germ line cells. Therefore, a new pattern of
imprinting can be made with each generation.
Genes are imprinted differently depending on the parental origin of the chromosome that
contains them. In mice, the insulin-like growth factor 2 gene undergoes imprinting. The
protein encoded by this gene helps to regulate body size. Mice that possess two
functional copies of this gene are larger than those with two mutant copies. The size of
mice that are heterozygous at this locus depends on the parent from which the wild type
allele came. If the functional allele originated from the mother, the offspring will exhibit
dwarfism, whereas a paternal allele will generate a normal sized mouse. This is because
the maternal Igf2 gene is imprinted. Imprinting results in the inactivation of the Igf2 gene
on the chromosome passed down by the mother.
Imprints are formed due to the differential methylation of paternal and maternal alleles.
This results in differing expression between alleles from the two parents. Sites with
significant methylation are associated with low levels of gene expression. Higher gene
expression is found at unmethylated sites. In this mode of inheritance, phenotype is
determined not only by the specific allele transmitted to the offspring, but also by the sex
of the parent that transmitted it.
Individuals who possess cells with genetic differences from the other cells in their body
are termed mosaics. These differences can result from mutations that occur in different
tissues and at different periods of development. If a mutation happens in the non-gamete
forming tissues, it is characterized as somatic. Germline mutations occur in the egg or
sperm cells and can be passed on to offspring. Mutations that occur early on in
development will affect a greater number of cells and can result in an individual that can
be identified as a mosaic strictly based on phenotype.
Mosaicism also results from a phenomenon known as X-inactivation. All female
mammals have two X chromosomes. To prevent lethal gene dosage problems, one of
these chromosomes is inactivated following fertilization. This process occurs randomly
for all of the cells in the organism’s body. Because a given female’s two X chromosomes
will almost certainly differ in their specific pattern of alleles, this will result in differing
cell phenotypes depending on which chromosome is silenced. Calico cats, which are
almost all female, demonstrate one of the most commonly observed manifestations of this
Trinucleotide repeat disorders
Trinucleotide repeat disorders also follow a non-Mendelian pattern of inheritance. These
diseases are all caused by the expansion of microsatellite tandem repeats consisting of a
stretch of three nucleotidesIn normal individuals, the number of repeated units is
relatively low. With each successive generation, there is a chance that the number of
repeats will expand. As this occurs, progeny can progress to permutation and ultimately
affected status. Individuals with a number of repeats that falls in the permutation range
have a good chance of having affected children. Those who progress to affected status
will exhibit symptoms of their particular disease. Prominent trinucleotide repeat disorders
include Fragile X syndrome and Huntington's disease. In the case of Fragile X syndrome
it is thought that the symptoms result from the increased methylation and accompanying
reduced expression of the fragile X mental retardation gene in individuals with a
sufficient number of repeats