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Ch. 21 - Genomic Analysis
Chapter 20, Problem 24

Dominguez et al. (2004) suggest that by studying genes that determine growth and tissue specification in the eye of Drosophila, much can be learned about human eye development.

What evidence indicates that the eyeless gene is part of a developmental network?

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1
Identify the role of the eyeless gene in Drosophila development, noting that it is crucial for eye formation.
Understand that the eyeless gene is homologous to the Pax6 gene in humans, which is also essential for eye development, indicating a conserved function across species.
Recognize that mutations in the eyeless gene result in the absence of eyes in Drosophila, demonstrating its necessity in the developmental network for eye formation.
Consider experiments where ectopic expression of the eyeless gene in non-eye tissues of Drosophila leads to the formation of eye structures, showing its sufficiency in initiating eye development.
Review genetic interaction studies that show the eyeless gene interacts with other genes in a network, coordinating the complex process of eye development.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Eyeless Gene

The eyeless gene in Drosophila is a critical gene that regulates eye development. It encodes a transcription factor that initiates the formation of eye tissues. Mutations in this gene can lead to the absence of eyes, demonstrating its essential role in ocular development. Understanding its function provides insights into similar genetic mechanisms in other organisms, including humans.
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Mapping Genes

Developmental Gene Networks

Developmental gene networks are interconnected groups of genes that work together to control the development of specific tissues and organs. These networks involve signaling pathways and regulatory interactions that ensure proper timing and spatial expression of genes during development. The eyeless gene is part of such a network, influencing and being influenced by other genes that contribute to eye formation.
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Segmentation Genes

Conservation of Genetic Pathways

Conservation of genetic pathways refers to the phenomenon where similar genetic mechanisms are preserved across different species through evolution. This concept suggests that studying model organisms like Drosophila can reveal fundamental biological processes applicable to humans. Evidence of the eyeless gene's role in eye development in fruit flies supports the idea that analogous genes may function similarly in human eye development.
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Related Practice
Textbook Question

Yeager, M., et al. [(2007) Nature Genetics 39:645–649] and Sladek, R., et al. [(2007) Nature 445:881–885] have used single-nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS) to identify novel risk loci for prostate cancer and Type 2 diabetes, respectively. Each study suggests that disease-risk genes can be identified that significantly contribute to the disease state. Given your understanding of such complex diseases, what would you determine as reasonable factors to consider when interpreting the results of GWAS?

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Textbook Question
Comparisons between human and chimpanzee genomes indicate that a gene that may function as a wild-type or normal gene in one primate may function as a disease-causing gene in another [The Chimpanzee Sequencing and Analysis Consortium (2005). Nature 437:69–87]. For instance, the PPARG locus (regulator of adipocyte differentiation) is a wild-type allele in chimps but is clearly associated with Type 2 diabetes in humans. What factors might cause this apparent contradiction? Would you consider such apparent contradictions to be rare or common? What impact might such findings have on the use of comparative genomics to identify and design therapies for disease-causing genes in humans?
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Textbook Question

Dominguez et al. (2004) suggest that by studying genes that determine growth and tissue specification in the eye of Drosophila, much can be learned about human eye development.

What evidence suggests that genetic eye determinants in Drosophila are also found in humans? Include a discussion of orthologous genes in your answer.

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Textbook Question
Genomic sequencing has opened the door to numerous studies that help us understand the evolutionary forces shaping the genetic makeup of organisms. Using databases containing the sequences of 25 genomes, scientists examined the relationship between GC content and global amino acid composition [Kreil, D. P., and Ouzounis, C. A. (2001) Nucl. Acids Res. 29:1608–1615]. They found that it is possible to identify thermophilic species on the basis of their amino acid composition alone, which suggests that evolution in a hot environment selects for a certain whole organism amino acid composition. In what way might evolution in extreme environments influence genome and amino acid composition? How might evolution in extreme environments influence the interpretation of genome sequence data?
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Textbook Question

Whole-exome sequencing (WES) is helping physicians diagnose a genetic condition that has defied diagnosis by traditional means. The implication here is that exons in the nuclear genome are sequenced in the hopes that, by comparison with the genomes of nonaffected individuals, a diagnosis might be revealed.

What are the strengths and weaknesses of this approach?

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Textbook Question

Whole-exome sequencing (WES) is helping physicians diagnose a genetic condition that has defied diagnosis by traditional means. The implication here is that exons in the nuclear genome are sequenced in the hopes that, by comparison with the genomes of nonaffected individuals, a diagnosis might be revealed.

If you were ordering WES for a patient, would you also include an analysis of the patient's mitochondrial genome?

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