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Polygenic Traits

Introduces physical characteristics caused by multiple genes.

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    Polygenic Traits


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      Introduces Polygenic traits and includes examples.

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      Vocabulary

      Authors:
      Jessica Harwood
      Douglas Wilkin, Ph.D.

      Contributors:
      Doris Kraus, Ph.D.
      Niamh Gray-Wilson
      Jean Brainard, Ph.D.
      Sarah Johnson
      Jane Willan
      Corliss Karasov

      Editors:
      Douglas Wilkin, Ph.D.

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      Polygenic Traits

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      SCI.BIO.214 (Polygenic Traits – Life Science)

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      Science Biology Classical and molecular genetics Variations on Mendelian genetics

      Variations on Mendelian genetics

        • Worked example: Punnett squares
        • Variations on Mendel's laws (overview)
        • Multiple alleles, incomplete dominance, and codominance
        • Pleiotropy and lethal alleles
        • Polygenic inheritance and environmental effects
          This is the currently selected item.

        • Practice: Non-Mendelian genetics
        Next tutorial
        Chromosomal basis of genetics

      Science Biology Classical and molecular genetics Variations on Mendelian genetics

      Polygenic inheritance and environmental effects

      Traits that are controlled by multiple genes and/or influenced by the environment. Penetrance and expressivity.

      How is height inherited?

      If what you're really interested in is human genetics, learning about Mendelian genetics can sometimes be frustrating. You'll often hear a teacher use a human trait as an example in a genetics problem, but then say, "that's an oversimplification" or "it's much more complicated than that." So, what's actually going on with those interesting human traits, such as eye color, hair and skin color, height, and disease risk?
      As an example, let's consider human height. Unlike a simple Mendelian characteristic, human height displays:
      • Continuous variation. Unlike Mendel's pea plants , humans don’t come in two clear-cut “tall” and “short” varieties. In fact, they don't even come in four heights, or eight, or sixteen. Instead, it’s possible to get humans of many different heights, and height can vary in increments of inches or fractions of inches

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        Histogram showing height in inches of male high school seniors in a sample group. The histogram is roughly bell-shaped, with just a few individuals at the tails (60 inches and 77 inches) and many individuals in the middle, around 69 inches.

        The heights of a group of male high school seniors. Image modified from " Continuous variation: Quantitative traits ," by J. W. Kimball ( CC BY 3.0 )
      • A complex inheritance pattern. You may have noticed that tall parents can have a short child, short parents can have a tall child, and two parents of different heights may or may not have a child in the middle. Also, siblings with the same two parents may have a range of heights, ones that don't fall into distinct categories.
      Simple models involving one or two genes can't accurately predict all of these inheritance patterns. How, then, is height inherited?
      Height and other similar features are controlled not just by one gene, but rather, by multiple (often many) genes that each make a small contribution to the overall outcome. This inheritance pattern is sometimes called polygenic inheritance (poly– = many). For instance, a recent study found over 400 genes linked to variation in height

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      When there are large numbers of genes involved, it becomes hard to distinguish the effect of each individual gene, and even harder to see that gene variants (alleles) are inherited according to Mendelian rules. In an additional complication, height doesn’t just depend on genetics: it also depends on environmental factors, such as a child’s overall health and the type of nutrition he or she gets while growing up.
      In this article, we’ll examine how complex traits such as height are inherited. We'll also see how factors like genetic background and environment can affect the phenotype (observable features) produced by a particular genotype (set of gene variants, or alleles).

      Polygenic inheritance

      Human features like height, eye color, and hair color come in lots of slightly different forms because they are controlled by many genes, each of which contributes some amount to the overall phenotype. For example, there are two major eye color genes, but at least 14 other genes that play roles in determining a person’s exact eye color

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      Looking at a real example of a human polygenic trait would get complicated, largely because we’d have to keep track of tens, or even hundreds, of different allele pairs (like the 400 involved in height!). However, we can use an example involving wheat kernels to see how several genes whose alleles "add up" to influence the same trait can produce a spectrum of phenotypes

      1,4 ^1,4

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      In this example, there are three genes that make reddish pigment in wheat kernels, which we’ll call A, B, and C. Each comes in two alleles, one of which makes pigment (the capital-letter allele) and one of which does not (the lowercase allele). These alleles have additive effects: the aa genotype would contribute no pigment, the Aa genotype would contribute some amount of pigment, and the AA genotype would contribute more pigment (twice as much as Aa). The same would hold true for the B and C genes

      1,4 ^1,4

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      64-square Punnett square illustrating the phenotypes of the offspring of an AaBbCc x AaBbCc cross (in which each uppercase allele contributes one unit of pigment, while each lowercase allele contributes zero units of pigment).
      Of the 64 squares in the chart:
      1 square produces a very very dark red phenotype (six units of pigment)
      6 squares produce a very dark red phenotype (five units of pigment)
      15 squares produce a dark red phenotype (four units of pigment).
      20 squares produce a red phenotype (three units of pigment)
      15 squares produce a light red phenotype (two units of pigment)
      6 squares produce a very light red phenotype (one unit of pigment)
      1 square produces a white phenotype (no units of pigment)

      Diagram based on similar diagram by W. P. Armstrong

      5 ^5

      .

      Now, let’s imagine that two plants heterozygous for all three genes (AaBbCc) were crossed to one another. Each of the parent plants would have three alleles that made pigment, leading to pinkish kernels. Their offspring, however, would fall into seven color groups, ranging from no pigment whatsoever (aabbcc) and white kernels to lots of pigment (AABBCC) and dark red kernels. This is in fact what researchers have seen when crossing certain varieties of wheat

      1,4 ^1,4

      .

      This example shows how we can get a spectrum of slightly different phenotypes (something close to continuous variation) with just three genes. It’s not hard to imagine that, as we increased the number of genes involved, we’d be able to get even finer variations in color, or in another trait such as height.

      Environmental effects

      Human phenotypes—and phenotypes of other organisms—also vary because they are affected by the environment. For instance, a person may have a genetic tendency to be underweight or obese, but his or her actual weight will depend on diet and exercise (with these factors often playing a greater role than genes). In another example, your hair color may depend on your genes—until you dye your hair purple!
      One striking example of how environment can affect phenotype comes from the hereditary disorder phenylketonuria (PKU)

      6 ^6

      . People who are homozygous for disease alleles of the PKU gene lack activity of an enzyme that breaks down the amino acid phenylalanine. Because people with this disorder cannot get rid of excess phenylalanine, it rapidly builds up to toxic levels in their bodies

      7 ^7

      .

      If PKU is not treated, the extra phenylalanine can keep the brain from developing normally, leading to intellectual disability, seizures, and mood disorders. However, because PKU is caused by the buildup of too much phenylalanine, it can also be treated in a very simple way: by giving affected babies and children a diet low in phenylalanine

      8 ^8

      .

      If people with phenylketonuria follow this diet strictly from a very young age, they can have few, or even no, symptoms of the disorder. In many countries, all newborns are screened for PKU and similar genetic diseases shortly after birth through a simple blood test, as shown in the image above.

      _Image credit: " Phenylketonuria testing ," by Eric T. Sheler, USAF Photographic Archives (public domain)._

      Variable expressivity, incomplete penetrance

      Even for characteristics that are controlled by a single gene, it’s possible for individuals with the same genotype to have different phenotypes. For example, in the case of a genetic disorder, people with the same disease genotype may have stronger or weaker forms of the disorder, and some may never develop the disorder at all.
      In variable expressivity, a phenotype may be stronger or weaker in different people with the same genotype. For instance, in a group of people with a disease-causing genotype, some might develop a severe form of the disorder, while others might have a milder form. The idea of expressivity is illustrated in the diagram below, with the shade of green representing the strength of the phenotype.

      [Example]
      The genetic disorder retinoblastoma causes cancerous tumors of the eyes, but the disease varies in severity and speed of onset. Children with retinoblastoma may develop tumors in just one eye or in both eyes, and the tumors may appear more quickly or slowly after birth

      9 ^9

      .

      Narrow expressivity: all six squares are dark green.
      Variable expressivity: the six squares are various shades of green.
      The squares in each example are intended to represent individuals of the same genotype for the gene of interest.

      Illustration modeled after similar image by Steven M. Carr

      10 ^10

      .

      In incomplete penetrance, individuals with a certain genotype may or may not develop a phenotype associated with the genotype. For example, among people with the same disease-causing genotype for a hereditary disorder, some might never actually develop the disorder. The idea of penetrance is illustrated in the diagram below, with green or white color representing the presence or absence of a phenotype.

      [Example]
      Some mutations in the retinoblastoma gene have high penetrance, but others have lower (incomplete) penetrance. For mutations in this latter category, some family members with the mutation are normal, while others develop retinoblastoma tumors

      6,11 ^6,11

      .

      Complete penetrance: all six squares are dark green.
      Incomplete penetrance: three of the squares are dark green, and three of the squares are white.
      The squares in each example are intended to represent individuals of the same genotype for the gene of interest.

      Illustration modeled after similar image by Steven M. Carr

      10 ^10

      .

      What causes variable expressivity and incomplete penetrance? Other genes and environmental effects are often part of the explanation. For example, disease-causing alleles of one gene may be suppressed by alleles of another gene elsewhere in the genome, or a person's overall health may influence the strength of a disease phenotype

      11 ^11

      .

      [Attribution and references]
      This article is licensed under a CC BY-NC-SA 4.0 license.

      Works cited:

      1. Kimball, J. W. (2011, March 8). Continuous variation: Quantitative traits. Retrieved from http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/Q/QTL.html .
      2. Wood, A. R., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., … Frayling, T. M. (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics, 46, 1173-1186. http://dx.doi.org/10.1038/ng.3097 .
      3. White, D. and Rabago-Smith, M. (2011). Genotype-phenotype associations and human eye color. Journal of Human Genetics, 56, 5-7. http://dx.doi.org/10.1038/jhg.2010.126 .
      4. Department of Agronomy, Iowa State University. (2016). Inheritance of a quantitative trait. Retrieved July 26, 2016 from https://masters.agron.iastate.edu/classes/527/lesson07/detail/kernelColor.html .
      5. Armstrong, W. P. (n.d.). Continuous variation and Rh blood factor. In Wayne's Word. Retrieved July 26, 2016 from http://waynesword.palomar.edu/lmexer5.htm .
      6. Bergmann, D. C. (2011). Variations on and complications of the basic Mendelian rules. In Genetics lecture notes. Biosci41, Stanford University, 10.
      7. PAH. (2008). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/gene/PAH .
      8. Phenylketonuria. (2012). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/condition/phenylketonuria .
      9. National Cancer Institute. (2015, August 14). Retinoblastoma treatment – for health professionals. In Cancer types. Retrieved from http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq .
      10. Carr, S. M. (2014). Penetrance versus expressivity. Retrieved from https://www.mun.ca/biology/scarr/Penetrance_vs_Expressivity.html .
      11. Kelly, Jane. (2015, September 14). Retinoblastoma. In OMIM. Retrieved from http://www.omim.org/entry/180200 .
      12. Griffiths, A. J. F., Miller, J. H., Suzuki, D. T., Lewontin, R. C., and Gelbart, W. M. (2000). Penetrance and expressivity. In An introduction to genetic analysis (7th ed.). Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK22090/ .

      References:

      Armstrong, W. P. (n.d.). Continuous variation and Rh blood factor. In Wayne's Word. Retrieved July 26, 2016 from http://waynesword.palomar.edu/lmexer5.htm .
      Bergmann, D. C. (2011). Variations on and complications of the basic Mendelian rules. In Genetics lecture notes. Biosci41, Stanford University, 8-12.
      Breeding for grain quality traits: The challenges of measuring phenotypes and identifying genotypes. (2015). In Plant and soil sciences eLibrary. Retrieved from http://passel.unl.edu/pages/informationmodule.php?idinformationmodule=1066416033&topicorder=12&maxto=13 .
      Carr, S. M. (2014). Penetrance versus expressivity. Retrieved from https://www.mun.ca/biology/scarr/Penetrance_vs_Expressivity.html .
      Department of Agronomy, Iowa State University. (2016). Inheritance of a quantitative trait. Retrieved July 26, 2016 from https://masters.agron.iastate.edu/classes/527/lesson07/detail/kernelColor.html .
      Duffy, D. L., Montgomery, G. W., Chen, W., Zhao, Z. Z., Le, L., James, M. R., … Sturm, R. A. (2007). A three–single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. American Journal of Human Genetics, 80(2), 241-252. http://dx.doi.org/10.1086/510885 .
      Griffiths, A. J. F., Miller, J. H., Suzuki, D. T., Lewontin, R. C., and Gelbart, W. M. (2000). Penetrance and expressivity. In An introduction to genetic analysis (7th ed.). Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK22090/ .
      Kelly, Jane. (2015, September 14). Retinoblastoma. In OMIM. Retrieved from http://www.omim.org/entry/180200 .
      Multifactorial traits: Genomics at the cellular and gene level. (n.d.). In MI genetics resource center. Retrieved from https://www.migrc.org/TeachersAndStudents/MultifactorialTraits.html
      National Cancer Institute. (2015, August 14). Retinoblastoma treatment – for health professionals. In Cancer types. Retrieved from http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq .
      NHS National Genetics and Genomics Education Centre (n.d.). In Genetic glossary. Retrieved from http://www.geneticseducation.nhs.uk/genetic-glossary/221-penetrance .
      Penetrance. (2015, November 13). Retrieved November 22, 2015 from Wikipedia: https://en.wikipedia.org/wiki/Penetrance .
      PAH. (2008). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/gene/PAH .
      Phenylketonuria. (2012). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/condition/phenylketonuria .
      Polygenic. (2015, November 18). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/glossary=polygenic .
      Polygenic inheritance. (n.d.). In BioNinja. Retrieved from www.vce.bioninja.com.au/aos-3-heredity/inheritance/polygenic-inheritance.html.
      Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B. (2011). Mendel and the gene idea. In Campbell biology (10th ed., pp. 267-291). San Francisco, CA: Pearson.
      What are reduced penetrance and variable expressivity? (2015, November 18). In Genetics home reference. Retrieved from http://ghr.nlm.nih.gov/handbook/inheritance/penetranceexpressivity .
      White, D. and Rabago-Smith, M. (2011). Genotype-phenotype associations and human eye color. Journal of Human Genetics, 56, 5-7. http://dx.doi.org/10.1038/jhg.2010.126 .
      Wood, A. R., Esko, T., Yang, J., Vedantam, S., Pers, T. H., Gustafsson, S., … Frayling, T. M. (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics, 46, 1173-1186. http://dx.doi.org/10.1038/ng.3097 .
      Zeratsky, K. (2015, October 6). My favorite diet soda has a warning about phenylalanine. Is phenylalanine bad for you? [answer]. In Nutrition and healthy eating. Retrieved from http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/phenylalanine/faq-20058361 .
      Zlotogora, J. (2003). Penetrance and expressivity in the molecular age. Genetics in Medicine, 5, 347-352. http://dx.doi.org/10.1097/01.GIM.0000086478.87623.69 .

      Variations on Mendelian genetics

        • Worked example: Punnett squares
        • Variations on Mendel's laws (overview)
        • Multiple alleles, incomplete dominance, and codominance
        • Pleiotropy and lethal alleles
        • Polygenic inheritance and environmental effects
          This is the currently selected item.

        • Practice: Non-Mendelian genetics
        Next tutorial
        Chromosomal basis of genetics
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      Pleiotropy and lethal alleles
      Non-Mendelian genetics
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      Non-Mendelian genetics

      Biology Dictionary

      Polygenic Traits

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      Polygenic Traits Definition

      Polygenic traits are traits that are controlled by multiple genes instead of just one. The genes that control them may be located near each other or even on separate chromosomes. Because multiple genes are involved, polygenic traits do not follow Mendel’s pattern of inheritance. Instead of being measured discretely, they are often represented as a range of continuous variation. Some examples of polygenic traits are height, skin color, eye color, and hair color.

      Traits, Phenotypes, and Genotypes

      To help understand polygenic traits, explanation of traits, phenotypes, and genotypes is necessary. A trait is any feature of an organism, such as eye color. A phenotype is the set of an organism’s physical characteristics. For example, a person’s hair color, skin color, and eye color are all part of their phenotype. It can also be used to describe the available forms of a trait. For example, eye color is a trait, while its possible phenotypes are brown, hazel, and blue.

      A genotype is an organism’s genetic makeup. For example, a person may have a certain form of a gene, called an allele, for a trait. Genotype influences phenotype; if one has certain alleles, they will have a certain physical appearance, such as brown eyes or blue eyes. A person’s phenotype is the result of all of the interactions of their genes, although it can also be influenced by environment (e.g. sun tanning).

      Non-Mendelian Inheritance

      Polygenic traits are complex and unable to be explained by simple Mendelian inheritance alone. Mendelian inheritance is involved when one particular gene controls for a trait, and the traits are discrete. It is named after Gregor Mendel, an Austrian monk and botanist who studied pea plants in the 19th Century. Many of the traits in Mendel’s pea plants showed either/or phenotypes. For example, they could have white or purple flowers, short or tall, or have wrinkly seeds or smooth. This is because each trait was represented by only one gene which had two alleles: dominant and recessive. If a plant had two dominant alleles, or one dominant and one recessive allele , the flowers were purple, while if it had two recessive alleles, the flowers were white.

      Polygenic traits also have dominant and recessive alleles, but so many genes play a role in an organism’s phenotype for these traits that the final result is the sum of many complex interactions. It can be hard or impossible to figure out one gene’s effect on a polygenic trait. Instead of being expressed in a ratio as single-gene traits are, polygenic traits are expressed continuously and usually form a bell curve when charted. For example, human skin color varies on a continuous gradient from light to dark, and it is not quantifiable; one’s skin color can only be compared to others for a sense of how light or dark his or her skin tone is. Some people have extremely light or extremely dark skin, but the majority of the world’s people do not, and fall somewhere in the middle.

      This figure depicts a bell curve. For a trait like skin color, shade (light to dark) would be on the X (horizontal) axis, and proportion of population would be on the Y (vertical) axis. When data form a bell curve, they are said to show a normal distribution.

      Dwustronny obszar krytyczny

      Examples of Polygenic Traits

      Height

      Human height is controlled by many genes; in fact, there are over 400 genes related to height, and all of these genes interact to make up a person’s phenotype. This is a very large number, but it makes sense because height is a compilation of the lengths of many different body parts, such as leg bones, the torso, and even the neck. Polygenic traits can also be influenced by an organism’s environment. If a person gets inadequate nutrition during childhood, they can have stunted growth and end up smaller and shorter than they would otherwise. It is estimated that 90% of a person’s adult height is controlled by genetics, and 10% is affected by the environment.

      This diagram shows the average offspring height based on the average height of both parents. Although tall parents tend to have tall children, there is a wide variation in the height that each child can be. On other words, tall parents can also have short children, and vice versa. This is represented by the many data points shown for each averaged height, with bigger data points representing a larger number of people.

      Galton height regress

      Skin Color

      In humans, skin color is influenced by many things, but the pigment melanin influences most of a person’s phenotype. In general, the more melanin a person has, the darker their skin is. Albino people produce no melanin at all. The body creates more melanin to protect against the sun’s UV rays, which is why skin darkens after prolonged sun exposure. The amount and type of melanin that a person produces, such as eumelanin, pheomelanin, and neuromelanin, is controlled by multiple genes, and the different types of melanin interact to form the final phenotype. For example, people with red hair have more pheomelanin and often have a pinkish skin tone.

      Eye Color

      There are 2 major human eye color genes, OCA2 and HERC2, but at least 13 other genes also play a role. The colored part of a person’s eye is the iris. It is a muscle that changes the size of the pupil in order to change the amount of light that is absorbed by the retina. A person’s eye color is determined by the pigmentation of their irises, but also by the way the cells in their irises scatter light. As with skin color, eye color is affected by the presence of melanin. People with brown eyes have a lot of melanin, while people with blue eyes have low melanin in the front part of the iris that is visible. Green eyes are caused by multiple factors; they are the result of a light brown iris combined with a blue tone given by light scattering.

      Related Biology Terms

      • Gene – The basic unit of heredity; made up of DNA, it is transferred by parent to offspring and codes for a specific part of the offspring’s phenotype.
      • Allele – A certain variant of a gene.
      • Melanin – A pigment in skin, hair, and eyes that affects its color.
      • Phenotype – Any part of an organism’s physical appearance.

      Quiz

      1. Which of these is NOT a polygenic trait?
      A. Height
      B. Skin color
      C. Eye color
      D. Widow’s peak

      Answer to Question #1
      D is correct. Having a widow’s peak, which is a V shaped front of the hairline, is not a polygenic trait. Individuals that have at least one dominant allele have a widow’s peak, while individuals with two recessive alleles have a hairline that is straight across the forehead.

      2. What does the pigment melanin influence?
      A. Skin color
      B. Eye color
      C. Hair color
      D. All of the above

      Answer to Question #2
      D is correct. Melanin is one of many substances that influence the color of human skin, eyes, and hair. The different forms of melanin are partially responsible for the variation in these traits.

      3. Which of these statements is true about human height?
      A. Tall people always have tall children.
      B. If the height of all the world’s individuals were plotted, the data would form a bell curve.
      C. Height is controlled by a single gene.
      D. Height is influenced by the amount of melanin produced.

      Answer to Question #3
      B is correct. The height of all the world’s individuals generally follows a normal distribution and would form a bell curve when charted. Some people are very short and others very tall, but the majority of the world’s population has a height somewhere in between.
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      Awesome…….

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      May 11, 2018 2:34 pm

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      Good information!

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      May 9, 2018 1:11 am

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      who wrote this great article?

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      November 12, 2017 10:44 am

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      great! thank you. i learned from you a lot.

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      September 13, 2017 5:48 am
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