Mendelian inheritance is based on the transmission of a single
gene on a dominant,
recessive or X-linked pattern. Discoveries on DNA structure, the
the genome and the observation that some characters and hereditary diseases
do not follow classical mendelian inheritance have led researchers to define
other patterns of transmission, referring particularly to multifactorial and
mitochondrial inheritance. Multifactorial inheritance is based on
of genes and environmental factors. Extra nuclear mitochondrial heredity can
only be transmitted by the mother whose cells contain a number of
Several factors can modify the expected individual
phenotypes.There will undoubtedly
be important advances in our knowledge of the pattern of
inheritance of characters
and diseases given a better understanding of gene structure and
of genes between them and with the environment.
Most frequent instance: Aa x AA ( marriage of an affected individual HEZ with a normal individual).
Examples of AD diseases :
Most frequent case: Aa x Aa (marriage of 2 normal heterozygotes).
Parental genotype: Aa x Aa
Examples of AR diseases:
Parental genotype : XX * xY
Parental genotype: Xx / xY
Rare situation if the mutation is severe.
Examples of RLX diseases :
Some individuals who carry the deleterious gene ( for
instance in an autosomal
dominant disease) do not present the expected phenotype: we
then say that
the penetrance is incomplete. The number of individuals who
carry a mutation
is less than the number of individuals who have an abnormal
is a quantitative estimate. In the neurofibromatosis type I, penetrance
is evaluated at approximately 80 % , but it is often difficult to detect
a mild form of the disease. An improved method to evaluate mutations in
those families will allow us to better understand this notion
C not to confound an isolate case due to a reduced penetrance
with a sporadic
case due to a mutation.
The phenotype can be more or less severe among affected
a variable expressivity of the deleterious gene. It is a
In Marfan syndrome for an identical familial gene mutation,
will have a severe form of the disease affecting the
and skeletal systems while for other individuals only the tall
arachnodactyly, without lens dislocation or aortic aneurysm,
will be noted.
--->Reduced penetrance and incomplete expressivity are
in autosomal dominant diseases.
Although they are present at birth several diseases manifest only later
in life. A normal physical examination of a 20 year old individual, from
a family at risk for Huntington disease, does not rule out the
that this individual is affected with the disease.
---> If the genetic defect is known in a family, the
will allow an early detection of the mutation or rule out this
before the expected age of onset of the disease.
---> Anticipation refers to a phenomenon characterizing
the earlier onset
of a disease in younger generations accompanied by more severe
The phenomenon is mainly observed in autosomal dominant
diseases, when there
is an increased elevation of triplet repeats from one generation to the
next as for instance in myotonic dystrophy (CTG) and Huntington disease
(CAG). In Friedreich ataxia, an autosomal recessive disease,
reports several families in which the increased triplet
repeats (GAA) from
one generation to the next is accompanied by an early onset
and a more severe
symptomatology. However one also finds in Fragile X syndrome, a X-linked
disease, a more severe expressivity in the presence of increased triplet
repeats without necessarily considering this an anticipation
In a number of genetic diseases the mutation can produce alterations in
more than one system. For instance in the < Moon Biedl > syndrome,
an autosomal recessive disease, malformations are seen in the
skeletal and ocular systems. The mutant gene effects are found
stages of the development.
The heterogeneity of mutations will lead to variable
Infrequently homologous chromosomes can have an uniparental
is called a maternal or paternal disomy for a pair of
For example an individual affected with cystic fibrosis had
one parent carrier
of a known mutation for which he was homozygous having
received two chromosomes
7 from the same parent carrier of this mutation and none from the other.
Disomies are rare and their effect is not well known yet.
During the course of development maternal and paternal genomes are not
equivalent but complementary due to an epigenetic phenomenon
Gene function can vary depending upon the maternal or
paternal origin of
the allele in question.
Gene action is sometimes regulated by more than one gene
acting as regulator.
A gene may have a normal structure but other genes in the
or the absence of co-factor(s) may be responsible for the inhibition of
a protein activity and the production of a genetic disease.
A number of genes susceptible to be at the origin of a cancer
cause a malformation syndrome.
A false paternity may sometimes be at the origin of an
incomplete or incorrect
family history. Doubt may arise about the paternity of an individual if
ongoing molecular studies do not find in the suspected father
of one or more DNA sequences.
Difficulties encountered sometime in the evaluation of a
pattern of transmission
of a disease may be due to diagnostic or classification errors. Several
groups of diseases like glycogenoses and mucopolysaccharidoses
a similar phenotype but a different enzymatic deficiency
confirmed by the
identification of a specific mutation for each one of them.
Examples of multifactorial diseases:
Mitochondrias come from ancestor anareobic
bacterias ;---> they have
their own DNA. We then have extranuclear DNA in our cells.
MITOCHONDRIAL DNA :
A mitochondrial gene disease is transmitted :
The term mitochondrial cytopathy may be ambiguous : the
cytopathies include not only the pathologies due to
mitochondrial gene mutations
but also those due to nuclear genes coding for proteins invoved
in the mitochondrial
metabolism (enzymes of the respiratoiry chain).
Examples of of mitochondrial hereditary diseases :
Dallaire L, Huret JL
Atlas of Genetics and Cytogenetics in Oncology and Haematology 2002-12-01
Mendelian and Atypical Patterns of Inheritance
Online version: http://atlasgeneticsoncology.org/teaching/30025/mendelian-and-atypical-patterns-of-inheritance