- Humans have 23 pairs of chromosomes:
- 22 pairs of autosomal chromosomes
- 1 pair of sex chromosomes
- Autosomal inheritance refers to the alleles located on autosomal chromosomes.
- 1 autosomal allele for each gene is passed down from each parent.
- Autosomal alleles are passed equally to both genders.
Autosomal recessive inheritance
Recessive alleles are only manifested when they are homozygous, which means that the individual inherited a recessive allele from each parent.
- In autosomal recessive inheritance, the carrier has to be homozygous for the trait to be inherited.
- Heterozygous individuals act as carriers but do not express the respective phenotype.
- Autosomal recessive diseases classically skip generations, which means phenotypically affected offspring usually have phenotypically unaffected parents.
- Consanguineous relationships are associated with a higher risk of inheritance of homozygous recessive diseases.
Autosomal dominant inheritance
Dominance is a key concept in Mendelian inheritance and classical genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics. Often, the dominant allele codes for a functional protein, whereas the recessive allele does not. If there is a dominant and recessive allele in a heterozygous genotype, only the dominant allele manifests.
- Dominant traits are expressed in both heterozygous and homozygous states, which means that only 1 dominant allele is needed to express the disease phenotype.
- Autosomal dominant diseases are seen in every generation.
- Homozygous individuals are often affected more severely than heterozygous ones.
Autosomal Recessive Inheritance
Examples of combinations
If 1 parent is homozygous and healthy and the other is heterozygous for the trait, all children will be phenotypically healthy but 50% will be carriers: Aa x AA = 50% AA + 50% Aa
If both parents are heterozygous for the trait, 25% of the children will have the disease, 50% will be heterozygous carriers, and 25% will be homozygous and healthy: Aa x Aa = 25% AA + 50% Aa + 25% aa
If a parent is heterozygous and the other is homozygous recessive, all children will be carriers, but 50% will have the disease: Aa x aa = 50% Aa + 50% aa
Autosomal recessive diseases
Albinism refers to a group of inherited disorders that result in the disruption of melanin production, causing hypopigmentation and visual impairment. The condition is classified according to the clinical phenotype. Oculocutaneous albinism results in hypopigmentation of the skin, eyes, and hair. Ocular albinism affects only the eyes.
- Disturbed melanin biosynthesis due to the absence of tyrosine hydroxylase
- Lack of pigmentation:
- White skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and hair
- Increased sensitivity to UV light
- Lack of phenylalanine hydroxylase, leading to phenylalanine elevation
- Signs: psychomotor retardation
- Treatment: a diet low in phenylalanine
Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency.
- Trinucleotide deletions on chromosome 7, which codes for the cystic fibrosis transmembrane conductance regulator (CFTR) transporter (chloride transporter)
- Chloride ions cannot be transported and added to secretions, which makes the secretions more viscous.
- Signs: respiratory infections and malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion disorders
Autosomal Dominant Inheritance
Examples of combinations
If 1 parent is homozygous for the trait and the other is homozygous recessive, all children will be heterozygous (phenotypically affected).
If both parents are heterozygous for the trait, 25% of the children will be homozygous dominant, 50% will be heterozygous, and 25% will be homozygous recessive. The phenotype will be expressed by 75% of the children.
If 1 parent is heterozygous for the trait, 50% of the children will be heterozygous (with the disease) and the other 50% will be homozygous recessive.
Autosomal dominant diseases
- Polydactyly: more than 5 fingers on a hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand
- Brachydactyly: unusually short fingers
- Ectrodactyly: lobster-claw hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand or split foot
- Disturbances in cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage formation
- Absence of growth plates results in disproportionate dwarfism with normal torso length but markedly short extremities.
- De novo mutations are responsible in 80% of cases.
Marfan syndrome is a genetic condition with autosomal dominant inheritance. Marfan syndrome affects the elasticity of connective tissues throughout the body, most notably in the cardiovascular, ocular, and musculoskeletal systems.
- Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the fibrillin gene
- Disturbed synthesis of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue
Huntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs.
- Caused by triplet (CAG) repeat expansions, which have destructive consequences for the neurons of the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia in the brain
- Penetrance depends on the number of triplet repeats, which means that more repeats lead to an earlier age of presentation with a more severe phenotype.
- Charlesworth, B., Charlesworth, D. (2017). Population genetics from 1966 to 2016. Heredity, 118, pp. 2–9. https://doi.org/10.1038/hdy.2016.55
- Jackson, M., Marks, L., May, G. H. W., & Wilson, J. B. (2018). The genetic basis of disease. Essays Biochem, 62(5), pp. 643–723. https://doi.org/10.1042/EBC20170053
- Letendre, P. Genetic Terminology. Retrieved October 18, 2021, from https://sites.ualberta.ca/~pletendr/tm-modules/genetics/70gen-term.html
- Raby, B. (2021). Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian). UpToDate. Retrieved October 18, 2021, from https://www.uptodate.com/contents/inheritance-patterns-of-monogenic-disorders-mendelian-and-non-mendelian