Inheritance of quantitative traits or polygenic inheritance refers to the inheritance of a phenotypic A phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior . Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two characteristic that varies in degree and can be attributed to the interactions between two or more genes A gene is a unit of heredity in a living organism. It is normally a stretch of DNA that codes for a type of protein or for an RNA chain that has a function in the organism. All living things depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic and their environment. Though not necessarily genes A gene is a unit of heredity in a living organism. It is normally a stretch of DNA that codes for a type of protein or for an RNA chain that has a function in the organism. All living things depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic themselves, quantitative trait loci (QTLs) are stretches of DNA that are closely linked to the genes that underlie the trait in question. QTLs can be molecularly identified (for example, with AFLP Amplified Fragment Length Polymorphism PCR is a PCR-based tool used in genetics research, DNA fingerprinting, and in the practice of genetic engineering. Developed in the early 1990’s by Keygene, AFLP uses restriction enzymes to cut genomic DNA, followed by ligation of adaptors to the sticky ends of the restriction fragments. A subset of the) to help map regions of the genome that contain genes involved in specifying a quantitative trait. This can be an early step in identifying and sequencing these genes.
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Quantitative traits
Polygenic inheritance, also known as quantitative or multifactorial inheritance refers to inheritance of a phenotypic A phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior . Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two characteristic (trait) that is attributable to two or more genes A gene is a unit of heredity in a living organism. It is normally a stretch of DNA that codes for a type of protein or for an RNA chain that has a function in the organism. All living things depend on genes, as they specify all proteins and functional RNA chains. Genes hold the information to build and maintain an organism's cells and pass genetic and their interaction with the environment. Unlike monogenic traits A genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by environmental factors. Most disorders are quite rare and affect one person in every several thousands or millions. Some types of recessive gene disorders confer an, polygenic traits do not follow patterns of Mendelian inheritance Mendelian inheritance is a set of primary tenets relating to the transmission of hereditary characteristics from parent organisms to their offspring; it underlies much of genetics. They were initially derived from the work of Gregor Mendel published in 1865 and 1866 which was "re-discovered" in 1900, and were initially very controversial (separated traits). Instead, their phenotypes typically vary along a continuous gradient depicted by a bell curve In probability theory and statistics, the normal distribution, or Gaussian distribution, is an absolutely continuous probability distribution whose cumulants of all orders above two are zero. The graph of the associated probability density function is “bell”-shaped, with peak at the mean, and is known as the Gaussian function or bell curve:[.[1]
An example of a polygenic trait is human skin color. Many genes factor into determining a person's natural skin color, so modifying only one of those genes changes the color only slightly. Many disorders with genetic components A genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by environmental factors. Most disorders are quite rare and affect one person in every several thousands or millions. Some types of recessive gene disorders confer an are polygenic, including autism Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their synapses connect and organize; how this occurs is not, cancer Cancer /ˈkænsər/ (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties, diabetes Diabetes mellitus, often simply referred to as diabetes—is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria , polydipsia (increased thirst) and numerous others. Most phenotypic characteristics are the result of the interaction of multiple genes.
Examples of disease processes generally considered to be results of multifactorial etiology Etiology is the study of causation, or origination. The word is derived from the Greek αἰτιολογία, aitiologia, "giving a reason for" (αἰτία, aitia, "cause"; and -λογία, -logia):
Congenital malformation
- Cleft palate Cleft lip and cleft palate (palatoschisis), which can also occur together as cleft lip and palate, are variations of a type of clefting congenital deformity caused by abnormal facial development during gestation. A cleft is a fissure or opening—a gap. It is the non-fusion of the body's natural structures that form before birth. Approximately 1[2] [3]
- Congenital dislocation of the hip Hip dysplasia, developmental dysplasia of the hip or congenital dysplasia of the hip (CDH) is a congenital or acquired deformation or misalignment of the hip joint[4]
- Congenital heart defects A congenital heart defect is a defect in the structure of the heart and great vessels of a newborn. Most heart defects either obstruct blood flow in the heart or vessels near it or cause blood to flow through the heart in an abnormal pattern, although other defects affecting heart rhythm (such as long QT syndrome) can also occur. Heart defects are
- Neural tube defects Neural tube defect is one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In about the 3rd or 4th weeks of pregnancy, specialized cells in the dorsal region begin to fuse and curl up which rolls
- Pyloric stenosis Pyloric stenosis is a condition that causes severe vomiting in the first few months of life. There is narrowing (stenosis) of the opening from the stomach to the intestines, due to enlargement (hypertrophy) of the muscle surrounding this opening (the pylorus, meaning "gate"), which spasms when the stomach empties. It is uncertain whether
- Talipes A clubfoot, or congenital talipes equinovarus , is a congenital deformity involving one foot or both. The affected foot appears rotated internally at the ankle. TEV is classified into 2 groups: Postural TEV or Structural TEV. Without treatment, persons afflicted often appear to walk on their ankles, or on the sides of their feet. It is a common
Adult onset diseases
- Diabetes Mellitus Diabetes mellitus —often simply referred to as diabetes—is a condition in which a person has a high blood sugar (glucose) level, either because the body doesn't produce enough insulin, or because body cells don't properly respond to the insulin that is produced. Insulin is a hormone produced in the pancreas which enables body cells to absorb[3]
- Cancer Cancer /ˈkænsər/ (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties[3]
- Epilepsy Epilepsy (from the Ancient Greek ἐπιληψία — "to seize") is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, with almost 9
- Glaucoma Glaucoma is a disease in which the optic nerve is damaged, leading to progressive, irreversible loss of vision. It is often, but not always, associated with increased pressure of the fluid in the eye
- hypertension Hypertension or high blood pressure is a chronic medical condition in which the systemic arterial blood pressure is elevated. It is the opposite of hypotension. It is classified as either primary (essential) or secondary. About 90–95% of cases are termed "primary hypertension", which refers to high blood pressure for which no medical
- Ischaemic heart disease Ischaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by ischaemia (reduced blood supply) to the heart muscle, usually due to coronary artery disease (atherosclerosis of the coronary arteries). Its risk increases with age, smoking, hypercholesterolaemia (high cholesterol levels), diabetes, hypertension (high
- Manic depression Bipolar disorder or manic–depressive disorder is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood clinically referred to as mania or, if milder, hypomania. Individuals who experience manic episodes also commonly experience depressive episodes or
- Schizophrenia Schizophrenia is a serious mental illness characterized by a disintegration of the process of thinking and of emotional responsiveness. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational dysfunction. Onset of symptoms typically occurs in
Multifactorially inherited diseases are said to constitute the majority of genetic disorders affecting humans which will result in hospitalization or special care of some kind[5] [6].
Multifactorial traits in general
Generally, multifactorial traits outside of illness contribute to what we see as continuous characteristics in organisms, such as height[5], skin color, and body mass[7]. All of these phenotypes are complicated by a great deal of interplay between genes and environment[5]. The continuous distribution of traits such as height and skin colour described above reflects the action of genes that do not quite show typical patterns of dominance and recessiveness. Instead the contributions of each involved locus are thought to be additive. Writers have distinguished this kind of inheritance as polygenic, or quantitative inheritance[8].
Thus, due to the nature of polygenic traits, inheritance will not follow the same pattern as a simple monohybrid A monohybrid cross is a cross between parents who are heterozygous at one locus; for example, Bb x Bb . Example: B = brown. b = blue. BB = Dark Brown. Bb = Brown (not blue). bb = Blue or dihybrid cross A dihybrid cross is a cross between F1 offspring of two individuals that differ in two traits of particular interest. For example: RRyy/rrYY or RRYY/rryy parents result in F1 offspring that are heterozygous for both R & Y[6]. Polygenic inheritance can be explained as Mendelian inheritance at many loci[5], resulting in a trait which is normally-distributed. If n is the number of involved loci, then the coefficients of the binomial expansion of (a + b)2n will give the frequency of distribution of all n allele combinations. For a sufficiently high n, this binomial distribution will begin to resemble a normal distribution. From this viewpoint, a disease state will become apparent at one of the tails of the distribution, past some threshold value. Disease states of increasing severity will be expected the further one goes past the threshold and away from the mean[8].
Heritable disease and multifactorial inheritance
A mutation resulting in a disease state is often recessive, so both alleles must be mutant in order for the disease to be expressed phenotypically. A disease or syndrome may also be the result of the expression of mutant alleles at more than one locus. When more than one gene is involved with or without the presence of environmental triggers, we say that the disease is the result of multifactorial inheritance.
The more genes involved in the cross, the more the distribution of the genotypes will resemble a normal, or Gaussian In probability theory and statistics, the normal distribution, or Gaussian distribution, is an absolutely continuous probability distribution whose cumulants of all orders above two are zero. The graph of the associated probability density function is “bell”-shaped, with peak at the mean, and is known as the Gaussian function or bell curve:[ distribution[5]. This shows that multifactorial inheritance is polygenic, and genetic frequencies can be predicted by way of a polyhybrid Mendelian Mendelian inheritance is a set of primary tenets relating to the transmission of hereditary characteristics from parent organisms to their offspring; it underlies much of genetics. They were initially derived from the work of Gregor Mendel published in 1865 and 1866 which was "re-discovered" in 1900, and were initially very controversial cross. Phenotypic frequencies are a different matter, especially if they are complicated by environmental factors.
The paradigm of polygenic inheritance as being used to define multifactorial disease has encountered much disagreement. Turnpenny (2004) discusses how simple polygenic inheritance cannot explain some diseases such as the onset of Type I diabetes mellitus, and that in cases such as these, not all genes are thought to make an equal contribution[8].
The assumption of polygenic inheritance is that all involved loci make an equal contribution to the symptoms of the disease. This should result in a normal curve distribution of genotypes. When it does not, then idea of polygenetic inheritance cannot be supported for that illness.
A cursory look at some examples
Examples of such diseases are not new to medicine. The above examples are well-known examples of diseases having both genetic and environmental components. Other examples involve atopic diseases such as eczema Atopic dermatitis (a type of eczema) is an inflammatory, chronically relapsing, non-contagious and pruritic skin disease. It has been given names like "prurigo Besnier," "neurodermitis," "endogenous eczema," "flexural eczema," "infantile eczema," and "prurigo diathsique" or dermatitis Atopic dermatitis (a type of eczema) is an inflammatory, chronically relapsing, non-contagious and pruritic skin disease. It has been given names like "prurigo Besnier," "neurodermitis," "endogenous eczema," "flexural eczema," "infantile eczema," and "prurigo diathsique"[5]; also spina bifida Spina bifida is a developmental birth defect caused by the incomplete closure of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through the opening in the bones. There may or may not be a fluid- (open spine) and anencephaly Anencephaly is a cephalic disorder that results from a neural tube defect that occurs when the cephalic end of the neural tube fails to close, usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp. Children with this disorder are born without a forebrain, the largest part of (open skull) are other examples[2]
While schizophrenia Schizophrenia is a serious mental illness characterized by a disintegration of the process of thinking and of emotional responsiveness. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational dysfunction. Onset of symptoms typically occurs in is widely believed to be multifactorially genetic by biopsychiatrists Biological psychiatry, or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics and physiology to investigate the biological bases of, no characteristic genetic markers have been determined with any certainty.
Is it multifactorially heritable?
It is difficult to ascertain if any particular disease is multifactorially genetic. If a pedigree chart A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next, most commonly humans, show dogs, and race horses. The word pedigree is a corruption of the French "pied de grue" or crane's foot, because the typical lines and split is taken of the patient's family and relations, and it is shown that the brothers and sisters of the patient have the disease, then there is a strong chance that the disease is genetic and that the patient will also be a genetic carrier. But this is not quite enough. It also needs to be proven that the pattern of inheritance is non-Mendelian. This would require studying dozens, even hundreds of different family pedigrees before a conclusion of multifactorial inheritance is drawn. This often takes several years.
If multifactorial inheritance is indeed the case, then the chance of the patient contracting the disease is reduced if only cousins and more distant relatives have the disease[2]. It must be stated that while multifactorially-inherited disease tends to run in families, inheritance will not follow the same pattern as a simple monohybrid A monohybrid cross is a cross between parents who are heterozygous at one locus; for example, Bb x Bb . Example: B = brown. b = blue. BB = Dark Brown. Bb = Brown (not blue). bb = Blue or dihybrid cross A dihybrid cross is a cross between F1 offspring of two individuals that differ in two traits of particular interest. For example: RRyy/rrYY or RRYY/rryy parents result in F1 offspring that are heterozygous for both R & Y[6].
If a genetic cause is suspected and little else is known about the illness, then it remains to be seen exactly how many genes are involved in the phenotypic expression of the disease. Once that is determined, the question must be answered: if two people have the required genes, why some people still don't express the disease. Generally, what makes the two individuals different are likely to be environmental factors. Due to the involved nature of genetic investigations needed to determine such inheritance patterns, this is not usually the first avenue of investigation one would choose to determine etiology.
Quantitative trait locus
A QTL for osteoporosis Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard on the human chromosome 20Typically, QTLs underlie continuous traits A trait is a distinct variant of a phenotypic character of an organism that may be inherited, environmentally determined or somewhere in between. For example, eye color is a character or abstraction of an attribute, while blue, brown and hazel are traits (those traits that vary continuously, e.g. height) as opposed to discrete traits (traits that have two or several character values, e.g. red hair in humans, a recessive trait, or smooth vs. wrinkled peas used by Mendel Gregor Johann Mendel was an Augustinian priest and scientist, who gained posthumous fame as the figurehead of the new science of genetics for his study of the inheritance of certain traits in pea plants. Mendel showed that the inheritance of these traits follows particular laws, which were later named after him. The significance of Mendel's work in his experiments).
Moreover, a single phenotypic A phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior . Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two trait is usually determined by many genes. Consequently, many QTLs are associated with a single trait.
A quantitative trait locus (QTL) is a region of DNA Deoxyribonucleic acid ( /diːˌɒksɨˌraɪbɵ.nuːˈkleɪ.ɪk ˈæsɪd/ (help·info)) (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of that is associated with a particular phenotypic A phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior . Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two trait A trait is a distinct variant of a phenotypic character of an organism that may be inherited, environmentally determined or somewhere in between. For example, eye color is a character or abstraction of an attribute, while blue, brown and hazel are traits - these QTLs are often found on different chromosomes A chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. The word chromosome comes from the Greek χρῶμα. Knowing the number of QTLs that explains variation in the phenotypic trait tells us about the genetic architecture Genetic architecture refers to the underlying genetic basis of a phenotypic trait. A synonymous term is the 'genotype-phenotype map', the way that genotypes map to the phenotypes of a trait. It may tell us that plant height is controlled by many genes of small effect, or by a few genes of large effect.
Another use of QTLs is to identify candidate genes underlying a trait. Once a region of DNA is identified as contributing to a phenotype, it can be sequenced. The DNA sequence of any genes in this region can then be compared to a database of DNA for genes whose function is already known.
In a recent development, classical QTL analyses are combined with gene expression profiling i.e. by DNA microarrays. Such expression QTLs (eQTLs) describe cis- and trans-controlling elements for the expression of often disease-associated genes. Observed epistatic effects have been found beneficial to identify the gene responsible by a cross-validation of genes within the interacting loci with metabolic pathway- and scientific literature databases.
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TheHeart.Org "There has been a real concern that despite larger and larger meta-analyses of genome-wide association data, for many polygenic traits only a small ...
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C = deposit pigment c = pigment not deposited Therefore gene 2 determines black or brown if genotypes for 2 is CC or Cc If cc white mice regardless of B or b Polygenic Inheritance the additive effect of two or more genes on a single phenotypic character Example skin colour Fig 13 13 page 251
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ue, 03 Apr 2007 19:23:00 GM
albinism. colorblindness. hemophilia. 12. how is skin color in humans related to . polygenic inheritance. ? 13. what is the diploid and haploid chromosome number in humans? 14. what are the fundamentals of x-linked inheritance? ...
