Transmission of Genes
Leon E. Rosenberg, Diane Drobnis Rosenberg, in Human Genes and Genomes, 2012
The Law of Independent Assortment
Mendel’s work with single characteristics demonstrated that alleles segregate during reproduction. He went on to study the simultaneous inheritance of two seemingly unrelated characteristics. How would two pairs of alleles segregate in a dihybrid cross? he asked. To answer this question, he employed, for instance, peas differing in color and shape [Figure 5.5]. First, he obtained true-breeding yellow round peas [YYRR] and true-breeding green wrinkled ones [yyrr]. He then crossed these parental [P1] varieties and found that all the F1 were yellow and round [as expected for doubly heterozygous plants—YyRr—whose phenotype expresses the dominant alleles]. When he self-crossed [fertilized the plant with its own pollen] the F1 plants, four phenotypes were evident in the F2: yellow round, yellow wrinkled, green round, and green wrinkled. That is, there were two parental types and two “new ones” produced in the dihybrid cross [recombinants]. In one experiment, typical of many, he found 315 yellow round peas, 101 yellow wrinkled, 108 green round, and 32 green wrinkled.
FIGURE 5.5. A typical dihybrid cross leading to the principle of independent assortment. Two different phenotypes were studied simultaneously [e.g., yellow/round and green/wrinkled]. As noted, the experimental design [P, F1, F2] was the same as used in the mono-hybrid cross shown in Figure 5.4. In the F1, all peas displayed both dominant characters—yellow and round. In the F2, the four possible phenotypes were recovered at the ratios shown on the right. The gene for yellow and the gene for round acted independently of one another; that is, they assorted.
From these data he proposed that segregation of one pair of alleles had no effect on the segregation of another pair—that gene pairs assort independently. Said another way, the presence of an allele for one gene has no effect on the presence of an allele for a second gene. From the Punnett square in Figure 5.5, the proof for this thesis is at hand. In the gametes of the F1 self -cross [female and male], four genotypes are expected [YR, Yr, yR, yr]—identical in female and male. Sixteen genotypes, then, are predicted in the F2. Of these, 9/16 are yellow round, 3/16 yellow wrinkled, 3/16 green round, and 1/16 green wrinkled. Note that this conforms almost exactly to the observed numbers and phenotypes of the peas in the typical experiment noted above. As important, the ratio of yellow to green, or round to wrinkled, was 12 : 4 [or 3 : 1], exactly as in the monohybrid crosses discussed earlier.
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Transmission Genetics
J.R. Fabian, in Encyclopedia of Genetics, 2001
Independent Assortment
Mendel also studied crosses where he followed the segregation of two separate pairs of contrasting traits. The initial cross involved two homozygous parents that differed in two different traits represented by the cross AABB×aabb. The F1 offspring of this cross were dihybrid plants of the genotype AaBb. Mendel performed a dihybrid cross and examined the phenotypes and genotypes of F2 plants. Mendel observed that each pair of traits was inherited independently. He observed a 3:1 ratio of dominant to recessive trait when the A and B pairs of traits were considered separately, as independent crosses [Aa × Aa and Bb × Bb]. When considered together in one cross [AaBb × AaBb], the combinations of traits appeared in the phenotype ratio of 9/16 with both dominant traits, 3/16 with one dominant trait, 3/16 with the other, and 1/16 with both recessive traits. This ratio is designated as Mendel's 9:3:3:1 dihybrid ratio and is based on probability events involving segregation, independent assortment, and random fertilization.
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The Muscular Dystrophies: Molecular Basis and Therapeutic Strategies
Ahlke Heydemann, ... Elizabeth M. McNally, in Biochimica et Biophysica Acta [BBA] - Molecular Basis of Disease, 2007
Myostatin is a TGFβ family member that is an inhibitor of skeletal muscle growth [52]. Because the myostatin null mouse [Mstn−/−] has an increased muscle mass due to hyperplasia and hypertrophy, it was bred to the mdx mouse model to determine its effect on muscular dystrophy [53]. The resultant mice had a reduced severity of disease as measured by muscle weight, grip strength, muscle fiber diameter, histology and hydroxyproline content. These findings have translated closer to therapy in that myostatin inhibitors also attenuate the mdx phenotype [54,55]. Although these results have been encouraging and lead to human clinical trials, a second dihybrid cross was undertaken which cautions against the positive results of the mdx/Mstn−/− data. The same myostatin null mutation was bred onto the laminin-deficient mice, dyW/dyW, a model for merosin deficient CMD. In this cross, increased muscle regeneration and muscle mass, due primarily to hyperplasia, were present. However, no improvement of muscle pathology and an increase in pre-weaning mortality was described [56]. The difference between the two models may relate to intrinsic pathologic defects between the two forms of muscular dystrophy. The more severe phenotype of the dyW/dyW mice and/or the lack of tolerance for decreased brown fat in the dyW/dyW mice may also contribute. An alternative strategy that would directly test the contribution of brown fat would utilize the cre-lox technology to eliminate myostatin shortly after birth, beyond the window where brown fat may be required [57]. Over-expression of a dominant negative myostatin exclusively in differentiated muscles may also reflect what can be achieved through pharmacologic inhibition [58].
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Science communication in the field of fundamental biomedical research
Sanjai Patel, ... Andreas Prokop, in Seminars in Cell & Developmental Biology, 2017
3.4 A lesson on classical genetics and the principal processes of scientific discovery
This lesson will soon be available. It addresses a number of GCSE and A-level specifications including cell division and cell cycle, genetic inheritance and an appreciation of how scientific knowledge is developed over time. It starts with examples of inherited diseases in humans, alerting to their genetic basis. Using low-cost microscopes [49], we then carry out an exercise on Drosophila mutations: students match genetic marker mutations of real flies to a set of drawings. We suggest two possible ways to continue from here: [1] We explain the practical uses of these marker mutations in contemporary research, for example in fly stock keeping. This involves application of Punnett squares and reaches into dihybrid crosses and even the use of transgenic technology and modern genetic markers by introducing chromosomes expressing green fluorescent protein. This learning outcome can also be achieved through a homework task we provide. [2] We exemplify a scientific discovery process through, step-by-step, working out with pupils how the white mutation, combined with knowledge of the time, led to the understanding that genes are located on chromosomes [50]. At the various steps, we formulate hypotheses which are then tested by applying Punnett squares. Since the white gene is located on the X-chromosome, we show pupils Ishihara plates used for testing colour blindness [51]: ∼10% of male pupils will be red-green colour blind illustrating that it is as an X-chromosomal trait and that understanding from Drosophila directly applies to humans. [3] Another possibility [which we so far only tested on extra-curricular school visits] is to explain how some marker mutations led to important scientific discoveries; for example, the important impact that the Notch mutation had on the biomedical sciences including development, stem cells and cancer [52]. To achieve differentiation, the PowerPoint file contains further flexible modules, including one on recombination and chromosomal mapping and maps.
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