The probability of an event is calculated by the number of times the event occurs divided by the total number of opportunities for the event to occur. A probability of one percent for some event indicates that it is guaranteed to occur, whereas a probability of zero 0 percent indicates that it is guaranteed to not occur, and a probability of 0.
To demonstrate this with a monohybrid cross, consider the case of true-breeding pea plants with yellow versus green seeds. The dominant seed color is yellow; therefore, the parental genotypes were YY for the plants with yellow seeds and yy for the plants with green seeds.
A Punnett square, devised by the British geneticist Reginald Punnett, is useful for determining probabilities because it is drawn to predict all possible outcomes of all possible random fertilization events and their expected frequencies.
Figure 8. To prepare a Punnett square, all possible combinations of the parental alleles the genotypes of the gametes are listed along the top for one parent and side for the other parent of a grid. The combinations of egg and sperm gametes are then made in the boxes in the table on the basis of which alleles are combining. Each box then represents the diploid genotype of a zygote, or fertilized egg. Because each possibility is equally likely, genotypic ratios can be determined from a Punnett square.
If the pattern of inheritance dominant and recessive is known, the phenotypic ratios can be inferred as well. For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele. In this case, only one genotype is possible in the F 1 offspring. All offspring are Yy and have yellow seeds. When the F 1 offspring are crossed with each other, each has an equal probability of contributing either a Y or a y to the F 2 offspring.
The result is a 1 in 4 25 percent probability of both parents contributing a Y , resulting in an offspring with a yellow phenotype; a 25 percent probability of parent A contributing a Y and parent B a y , resulting in offspring with a yellow phenotype; a 25 percent probability of parent A contributing a y and parent B a Y , also resulting in a yellow phenotype; and a 25 percent probability of both parents contributing a y , resulting in a green phenotype.
When counting all four possible outcomes, there is a 3 in 4 probability of offspring having the yellow phenotype and a 1 in 4 probability of offspring having the green phenotype. Using large numbers of crosses, Mendel was able to calculate probabilities, found that they fit the model of inheritance, and use these to predict the outcomes of other crosses. Observing that true-breeding pea plants with contrasting traits gave rise to F 1 generations that all expressed the dominant trait and F 2 generations that expressed the dominant and recessive traits in a ratio, Mendel proposed the law of segregation.
This law states that paired unit factors genes must segregate equally into gametes such that offspring have an equal likelihood of inheriting either factor.
For the F 2 generation of a monohybrid cross, the following three possible combinations of genotypes result: homozygous dominant, heterozygous, or homozygous recessive. The equal segregation of alleles is the reason we can apply the Punnett square to accurately predict the offspring of parents with known genotypes.
Beyond predicting the offspring of a cross between known homozygous or heterozygous parents, Mendel also developed a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote. Called the test cross, this technique is still used by plant and animal breeders. In a test cross, the dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic.
If the dominant-expressing organism is a homozygote, then all F 1 offspring will be heterozygotes expressing the dominant trait Figure 8. Alternatively, if the dominant-expressing organism is a heterozygote, the F 1 offspring will exhibit a ratio of heterozygotes and recessive homozygotes Figure 8. The cross between the true-breeding P plants produces F1 heterozygotes that can be self-fertilized.
The self-cross of the F1 generation can be analyzed with a Punnett square to predict the genotypes of the F2 generation. Given an inheritance pattern of dominant—recessive, the genotypic and phenotypic ratios can then be determined.
In pea plants, round peas R are dominant to wrinkled peas r. You do a test cross between a pea plant with wrinkled peas genotype rr and a plant of unknown genotype that has round peas. You end up with three plants, all which have round peas. From this data, can you tell if the parent plant is homozygous dominant or heterozygous?
You cannot be sure if the plant is homozygous or heterozygous as the data set is too small: by random chance, all three plants might have acquired only the dominant gene even if the recessive one is present. Independent assortment of genes can be illustrated by the dihybrid cross, a cross between two true-breeding parents that express different traits for two characteristics.
Consider the characteristics of seed color and seed texture for two pea plants, one that has wrinkled, green seeds rryy and another that has round, yellow seeds RRYY. Because each parent is homozygous, the law of segregation indicates that the gametes for the wrinkled—green plant all are ry , and the gametes for the round—yellow plant are all RY.
Therefore, the F 1 generation of offspring all are RrYy Figure 8. In pea plants, purple flowers P are dominant to white p , and yellow peas Y are dominant to green y.
What are the possible genotypes and phenotypes for a cross between PpYY and ppYy pea plants? How many squares would you need to complete a Punnett square analysis of this cross?
The former two genotypes would result in plants with purple flowers and yellow peas, while the latter two genotypes would result in plants with white flowers with yellow peas, for a ratio of each phenotype. The gametes produced by the F 1 individuals must have one allele from each of the two genes. For example, a gamete could get an R allele for the seed shape gene and either a Y or a y allele for the seed color gene.
It cannot get both an R and an r allele; each gamete can have only one allele per gene. The law of independent assortment states that a gamete into which an r allele is sorted would be equally likely to contain either a Y or a y allele.
Thus, there are four equally likely gametes that can be formed when the RrYy heterozygote is self-crossed, as follows: RY , rY , Ry , and ry. Qualitative variables were described using an estimation of the proportions. Variables with a normal distribution were analyzed by the t -test, while the Mann Whitney or Kruskal-Wallis tests were used for variables with a non-normal distribution.
Therefore, we used data from 1, visits patients; 3. To identify factors that influenced disease activity DAS28 as the dependent variable and disability HAQ as the dependent variable during the follow-up, we fitted two population-averaged models by generalized linear models nested by patient and visit using the xtgee command of Stata In addition, to confirm the results obtained for disease activity we generated an ordered logistic model using the ologit command of Stata.
The dependent variable was the disease activity level, using the cut-off points for DAS28 proposed by Prevoo et al. The analysis was modeled as described above for xtgee , with remission considered 0 and low, moderate and high disease activity represented as 1, 2 and 3. The ordered logistic analysis estimates cut-off points that aid the interpretation of the coefficients for each independent variable according to the levels of the dependent variable.
At baseline, patients with definitive RA exhibited increased disease activity and disability, and higher acute phase reactant values than patients with UA Table 1. However, UA patients were younger and tended to exhibit shorter disease duration than RA patients Table 1.
To confirm our findings and obtain additional information, we analyzed the effects of these variables when disease activity is categorized as remission, or as low, moderate or high disease activity.
By contrast, the presence of a T allele of rs in PTPN22 was associated with more visits at weaker disease activity or remission Figure 2B. Using this approach, multivariate analysis revealed a stronger association between the ACPA and TT genotype of rs in STAT4 and increased levels of disease activity, without significant changes in the contribution of the other independent variables when compared with the previous model gender, age, etc.
In addition, the cut-off points obtained in the ordered logistic regression model rows at the bottom of Table 3 suggest that variables with positive coefficients, such as ACPA, gender or TT genotype of rs in STAT4, increased disease activity to moderate or high levels, while those with negative coefficients, such as the minor allele of rs in PTPN22 , decreased the disease activity to the level of remission.
As expected, disability was significantly correlated with DAS28 values. Moreover, female gender and older age were associated with significantly higher HAQ values. To the best of our knowledge, this is the first study demonstrating the influence of the STAT4 polymorphism rs on disease course and disability in EA. Moreover, the minor allele of rs has also been associated with severe disease in patients with systemic lupus erythematosus [18].
Therefore, the more intense disease activity observed in patients who were homozygous for the rs T allele may be associated with increased sensitivity to IL, IL or interferons. By contrast, the presence of the minor allele of rs in PTPN22 was associated with a trend towards diminished disease activity. The functional effect of this polymorphism is open to debate, although most studies suggest that the allele promotes a gain of function and hence, an increased threshold for T cell receptor TCR signaling that may lead to defective deletion of autoreactive clones in the thymus [3] , [19].
Our results could support this hypothesis, suggesting that once self-tolerance is broken in patients with the rs T allele, autoreactive lymphocytes are activated less efficiently through TCR. Surprisingly, the presence of the SE was not associated with increased disease activity or disability, probably due to the inclusion of ACPA in the statistical models.
However, excluding this variable revealed no significant association between the presence of the SE and a worse outcome data not shown. Although unexpected, there may be several explanations for this finding: a a proportion of SE carriers were non-smokers and thus, they did not develop ACPA; b some patients may be heterozygous carriers of SE and carry protective DRB1 alleles; or c SE may be less important in RA patients from southern Europe than northern Europe.
As with PTPN22 , specific genetic factors may confer a risk of developing the disease, and while some may only modify disease severity, others may be involved in both processes. Few studies have evaluated the effects of genetic markers that confer a risk of developing RA on disease activity and disability.
The conflicting findings of this and our study may be due to the differences in study design. As opposed to the cross-sectional cohort study carried out previously, we performed a longitudinal study with almost 4 observations per patient, providing a more detailed picture of disease activity and disability. Our study involved patients from 2 clinical centers, a confounding variable for which the analysis of disease activity was adjusted.
This is particularly important given the poor reproducibility of tender and swollen joint counts [20]. Furthermore, the study of Morgan and coworkers only adjusted the analysis for disease duration, which was longer than in our cohort.
In summary, our data suggest that homozygosity for the STAT4 rs minor allele is associated with a poorer disease course and greater disability than homozygosity for the common allele of this variant. We propose that the rs polymorphism may be used as a molecular tool to identify patients that may benefit from early aggressive treatment.
We thank Dr. Loreto Carmona for her critical reading of the study and Mark Sefton for his editorial assistance. We also thank Ms. Belen Diaz-Sanchez for her technical support. Mendel bred peas and noticed he could cross-pollinate them in certain ways to get green or yellow seeds. Today, the field of genetics is breaking new ground searching for new ways to treat disease or develop crops more resistant to insects or drought.
Empower your students to learn about genetics with this collection of resources. Genetic variation is the presence of differences in sequences of genes between individual organisms of a species.
It enables natural selection, one of the primary forces driving the evolution of life. Genes are units of hereditary information. A gene is a section of a long molecule called deoxyribonucleic acid DNA.
Join our community of educators and receive the latest information on National Geographic's resources for you and your students. Skip to content. Image Female portrait Many physical traits like hair color and texture, eye color, and skin color are determined by the genotypes that parents pass down to their children.
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