Autosomal Recessive and Autosomal Dominant Inheritance

Definitions

Overview

• Humans have 23 pairs of chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure:
  • 22 pairs of autosomal chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure
  • 1 pair of sex chromosomes Sex chromosomes The homologous chromosomes that are dissimilar in the heterogametic sex. There are the X chromosome, the Y chromosome, and the w, z chromosomes (in animals in which the female is the heterogametic sex (the silkworm moth bombyx mori, for example)). In such cases the w chromosome is the female-determining and the male is zz. Basic Terms of Genetics
• Autosomal inheritance refers to the alleles located on autosomal chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure.
• 1 autosomal allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics for each gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics 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 Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics from each parent.

• In autosomal recessive inheritance, the carrier Carrier Vaccination has to be homozygous for the trait to be inherited.
• Heterozygous individuals act as carriers Carriers The Cell: Cell Membrane but do not express the respective phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics.
• 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 Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics codes for a functional protein, whereas the recessive allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics does not. If there is a dominant and recessive allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics in a heterozygous genotype Genotype The genetic constitution of the individual, comprising the alleles present at each genetic locus. Basic Terms of Genetics, only the dominant allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics manifests.

• Dominant traits are expressed in both heterozygous and homozygous states, which means that only 1 dominant allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics is needed to express the disease phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics.
• 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 Carriers The Cell: Cell Membrane: Aa AA Amyloidosis x AA AA Amyloidosis = 50% AA AA Amyloidosis + 50% Aa AA Amyloidosis

If both parents are heterozygous for the trait, 25% of the children will have the disease, 50% will be heterozygous carriers Carriers The Cell: Cell Membrane, and 25% will be homozygous and healthy: Aa AA Amyloidosis x Aa AA Amyloidosis = 25% AA AA Amyloidosis + 50% Aa AA Amyloidosis + 25% aa AA Amyloidosis

If a parent is heterozygous and the other is homozygous recessive, all children will be carriers Carriers The Cell: Cell Membrane, but 50% will have the disease: Aa AA Amyloidosis x aa AA Amyloidosis = 50% Aa AA Amyloidosis + 50% aa AA Amyloidosis

Autosomal recessive diseases

• Albinism Albinism 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. Albinism:
  • Disturbed melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology due to the absence of tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids 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. Skin: Structure and Functions and hair
    • Increased sensitivity to UV light UV light That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris
• Phenylketonuria:
  • Lack of phenylalanine hydroxylase Phenylalanine hydroxylase An enzyme of the oxidoreductase class that catalyzes the formation of l-tyrosine, dihydrobiopterin, and water from l-phenylalanine, tetrahydrobiopterin, and oxygen. Synthesis of Nonessential Amino Acids, leading to phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids elevation
  • Signs: psychomotor retardation
  • Treatment: a diet low in phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids
• Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans:
  • Trinucleotide deletions on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 7, which codes for the cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans transmembrane conductance regulator (CFTR) transporter ( chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes transporter)
  • Chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes ions cannot be transported and added to secretions, which makes the secretions more viscous.
  • Signs: respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. 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 Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics 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 Polydactyly A congenital anomaly of the hand or foot, marked by the presence of supernumerary digits. Physical Examination of the Newborn: 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: Anatomy
• 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: Anatomy or split foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy
• Achondroplasia:
  • 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: Histology formation
  • Absence of growth plates Growth Plates The area between the epiphysis and the diaphysis within which bone growth occurs. Osteosarcoma results in disproportionate dwarfism with normal torso length but markedly short extremities.
  • De novo mutations are responsible in 80% of cases.
• Marfan syndrome Marfan syndrome 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. Marfan Syndrome:
  • 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 Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
  • Disturbed synthesis Synthesis Polymerase Chain Reaction (PCR) 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: Histology
• Huntington disease Huntington disease 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. Huntington Disease:
  • Caused by triplet (CAG) repeat expansions, which have destructive consequences for the neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology 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: Anatomy in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
  • Penetrance Penetrance The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. Familial Juvenile Polyposis depends on the number of triplet repeats, which means that more repeats lead to an earlier age of presentation with a more severe phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics.