Study of Inheritance patterns in humans

Study of inheritance patterns plays an important role in understanding the features of genetic disorders. The traits or the characters get passed on from one generation to the next. This process is known as inheritance or heredity. With a combination of the father’s and mother’s genes, the zygote genetic material gets developed. Along with the healthy genes, there are chances of inheriting faulty or mutated genes or the carrier genes. Although there are no gene mutations, the incorrect chromosome segment exchange or chromosomal aberrations contribute to the risk of inheriting genetic disorders.

The inheritance of common traits follows either of the two patterns such as monogenic or polygenic inheritance. It is clear to study an inheritance pattern using a pedigree chart. The family history of the patient helps to collect the information of the inheritance pattern in a particular family and draw a pedigree chart. A pedigree is a sophisticated diagram showing the ancestral history of the patient and the relatives. The hereditary behavior of the genes depends on the type of the genetic material or a chromosome. There are two types of sex chromosomes such as X and Y chromosomes. X chromosomes are common in females. Y chromosomes are present in the males. The karyotype of a normal male is 46, XY. The karyotype of a normal female is 46, XX. Similarly, mitochondrial DNA follows maternal inheritance.  

Monogenic inheritance:

The monogenic or Mendelian inheritance determines the traits by a single gene. Hence, monogenic disorders are known as single gene disorders. There are two main kinds of monogenic disorders such as autosomal and sex-linked inheritance. Each of them follows the dominant or recessive pattern of inheritance.

Image 1: Autosomal dominant and autosomal recessive inheritance

1.     Autosomal dominant inheritance:

The phenotype gets expressed in those who have inherited only one copy of a particular gene mutation. The condition is heterozygous. It refers to a gene on one of the 22 pairs of autosomes (non-sex chromosomes). Thus, the disorder manifests only due to the presence of the affected gene in a single dose. Autosomal dominant inheritance affects both the sexes. The transmission of the affected gene follows male to male, female to female, male to female and female to male inheritance pattern. Almost every generation exhibits the trait. The traits do not skip between the generations. All the affected persons have at least one affected parent. Not all the offsprings suffer from the disorder. Some exhibit a normal phenotype or genotype. The marriage between the normal individuals prevents the mutant gene transmission to the next generation. Autosomal dominant cases equally exhibit the normal and affected individuals. Examples include Huntington’s disease, Myotonic dystrophies, and neurofibromatosis.

Autosomal recessive inheritance:

The gene or the mutant allele prevails in a double dose for expressing the trait. A heterozygous individual does not express the trait and is perfectly healthy.

Such an individual acts as a carrier and passes on the affected gene to the next generation. The trait prevails in the same generation between the siblings. However, it may be absent in the previous generations. Autosomal recessive inheritance equally affects both males and females. Mainly autosomes follow this kind of inheritance. The chances of manifesting the recessive disorder increase in the case of closely related parents. A pseudo-dominant inheritance results due to mating between an affected individual and a carrier. Thus the autosomal dominant inheritance affects 50% of the offspring. Examples of recessive inheritance include spinal muscular atrophy and cystic fibrosis.

Sex-linked inheritance:

Sex chromosomes mainly the X and Y chromosomes follow sex-linked inheritance pattern.

Image 2: X-linked inheritance pattern

X linked inheritance:

It occurs in the dominant or recessive form. A dominant mutation in the X chromosome is seen mostly in females. The male inheriting this condition does not survive as the gene is lethal. In an X linked dominant inheritance, mutant gene exists on the X chromosome. It gets expressed in the heterozygous females and males. It resembles an autosomal dominant inheritance because of the heterozygous pattern. However, there is a slight difference. The affected male transmits the traits to all the daughters and not to the sons. Hence, the trait distinguishes itself from the autosomal dominant trait. Vitamin-D resistant rickets, Xg blood groups, and hypophosphatemia are examples of X-linked dominant inheritance.

X-linked recessive inheritance involves the presence of a mutant gene. It leads to the expression of phenotype in males with the hemizygous condition (since males possess only one chromosome). In females, the expression of the phenotype occurs in homozygous individuals. Some of the genes present on the X chromosome resemble the genes on the autosomes. Examples include genes for color perception. The recessive traits express themselves only in a homozygous condition. A heterozygous female, though normal in the phenotype, becomes a carrier. She passes on the genes from the next generation. X-linked recessive inheritance dominates in males and affects less number of females. Mainly the unaffected carrier females pass on the traits to their sons. The affected male passes on the trait to all the daughters who will become carriers in future. The affected male does not transmit the trait to the sons since the affected genes are not present on the Y chromosome. Examples include DMD and hemophilia.

A very few cases involve Y linked inheritance. The H-Y histocompatibility antigen genes are present on a Y chromosome. There exist genes responsible for spermatogenesis. An affected individual transmits Y linked trait to all the sons and not to the daughters. Females never transmit the trait. Examples of Y linked inheritance include hairy ears.

Mitochondrial inheritance:

The mitochondrial DNA (mtDNA) follows maternal inheritance, meaning, it passes from the mother to the child. We all have our mother’s mitochondrial DNA. Since mitochondria constitute a part of the cytoplasm, this type of inheritance is also known as cytoplasmic inheritance. Mutations in mitochondrial DNA lead to cardiomyopathy, neuropathy, seizures, and encephalopathy.

 

Type of inheritance pattern	Study of familial disorders	Measures for prevention of the familial disorders
Autosomal dominant inheritance	Pedigree analysis Genetic testing Karyotyping	Prenatal diagnosis Genetic counseling
Autosomal recessive inheritance	Pedigree analysis Genetic testing Karyotyping	Genetic counseling Carrier detection Chromosome study Gene therapy (available for some cases)
Sex-linked inheritance	Pedigree analysis Karyotyping	Genetic counseling Adoption of the child or termination of the pregnancy may be adviced.
Mitochondrial inheritance	Shotgun testing Pedigree analysis A test involving 5-Mettetrahydrofolate in CSF	Genetic counseling Assisted reproduction technology

Table: Summary of different types of inheritance patterns and related familial disorders

Polygenic and Multifactorial inheritance:

Polygenic inheritance does not follow Mendelian inheritance pattern. A polygene involves a group of genes controlling a quantitative character. A polygenic character is a quantitatively variable phenotype. It depends on the interaction of numerous genes. Polygenic inheritance is also known as quantitative inheritance since it depends on cumulative gene action. Polygenic traits include intelligence, height, blood pressure, and eye color. Since many genes get involved, the inheritance pattern is known as multifactorial one.

References:
[1] Medical genetics, G.P. Pal
[2] Human Genetics, 3/e, Gangane
[3] Vogel and Motulsky's Human Genetics: Problems and Approaches, Friedrich Vogel, Gunter Vogel, Arno G. Motulsky
[4] Biology for the IB Diploma: Standard and Higher Level, Andrew Allott
[5] Principles of Medical Genetics, Thomas D. Gelehrter

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