Number of times the haplotype was observed in our sample of 851. groups of the world that are of darker average iris color (Frudakis et al. We sequenced with an ABI3700 using PE Applied Biosystems BDT chemistry and we deposited the sequences into a commercial relational database system (iFINCH, Geospiza, Seattle). Collin College Faculty Web Directory The first is that for most of the genes for which we identified marginally associated SNPs, multiple such SNPs were identified. P is for pigment and dimpled chins (D) are dominant over undimpled chins. Asterisks represent P values that remained significant after the correction for multiple tests and P values in italic are those that were statistically significant (P 0.05). Genetics Exam 3 Flashcards | Quizlet Hum Mol Genet 13, 447461 (2004). However, the penetrance of each of these alleles appears to be low and, in general, they appear to explain but a very small amount of the overall variation in iris colors within the human population (Spritz 1995). The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman Syndromes. Sturm, R., Duffy, D., Zhao, Z., Leite, F., Stark, M., Hayward, N. et al. 1998; Flanagan et al. Most of the haplotypes were even more dramatically associated with iris colors in a multiracial sample (data not shown), because many of the SNPs comprising them are good AIMs and variants associated with darker iris colors were enriched in those ancestral, The common haplotypes and diplotypes for the 16 iris color genes discussed in the text. MGG 1, 393394 (1908). In this pedigree use "A" to represent the dominant allele and "a" for the recessive allele.A PDF HUMAN SINGLE GENE TRAITS - Winston-Salem/Forsyth County Schools 2000), and adaptin 3B (AP3B) loci (Ooi et al. We identified 5 additional genes (ASIP, MC1R, POMC, and SILV) and one additional region (GSTT2-22q11.23) with haplotype and/or diplotypes, but not individual SNP alleles associated with iris colors. b List the possible genotypes for an individual with pigmented iris but Genetics of human iris colour and patterns - Sturm - 2009 - Pigment 1997; Smith et al. Most of the SNPs that we identified were on chromosome 15, which Eiberg and Mohr (1996) described from linkage analyses as the primary chromosome for the determination of brownness. As suggested by these authors, the candidate gene within the interval containing this locus (BEY2) is most likely the OCA2 gene, although the MYO5A gene is also present within this interval and, as shown here, associated with iris colors. The MC1R gene harbored haplotypes associated only with green color in our sample and the POMC gene harbored a single SNP with genotypes weakly associated with iris colors (no significant haplotypes or diplotypes were found). Relationship. As different genes may be transcribed in various cells, certain cells will produce more pigment or a different type of pigment than other adjacent cells. is called your "genotype" 2 matching alleles = "homozygous" 2 different alleles = "heterozygous" In heterozygous individuals, the allele that is "expressed" (seen in individual's appearance) is the "dominant" allele. This page titled 8.2: Human Traits Determined by Single Genes is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by Ellen Genovesi, Laura Blinderman, & Patrick Natale via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request. .. Kwon H Y, Bultman S J, Loffler C, Chen W-J, Furdon P J et al. Chromosome 15q harbored the majority (14/27) of the SNPs that were marginally associated with iris colors, and all but one of these 14 were found in two different genes: OCA2 and MYO5A (Table 2). HERC2/OCA2 rs12913832 and IRF4 rs12203592 influenced both eye colour and the number of iris pigmented lesions. genotype - all alleles present in the cell ; phenotype - physical appearance of a trait ; . Last, we thank the reviewers of this manuscript who suggested a number of important improvements. It is inherited or caused by somatic mutations within the cells.2 In addition, it can be caused by the inactivation of particular genes within the cells. A golden-brown iris indicates the mixture of both eumelanin and pheomelanin (produces the yellow color), and hazel is usually a mixture of brown and green or blue and green, depending on the shade. Most of the SNPs within a gene or region were in LD with others in that gene or region (|D| 0.05); only 32 SNP pairsin the MC1R (1 pair), OCA2 (27 pairs), TYR (2 pairs), and TYRP1 (2 pairs) geneswere found to be in linkage equilibrium (not shown). Zaumseger, D., Rothschild, M. & Schneider, P. SNPs for the analysis of human pigmentation genes--A comparative study. Forensic Sci Int: Genet. et al. There are two. Valenzuela, R., Henderson, M., Walsh, M., Garrison, N., Kelch, J., Cohen-Barak, O. et al. Each human somatic cell has 46 chromosomes in its nucleus. Representatives of the resulting PCR products were checked on an agarose gel, and first-round PCR product was diluted and then used as template for a second round of PCR. IRIS pigmentation is a complex genetic trait that has long interested geneticists, anthropologists, and the public at large. In the absence of melanin brown pigment, the iris is blue. 1997), and other genes (reviewed by Sturm et al. Even if the OCA2 gene contains the alleles for brown eyes, the SNP in intron 86 of HERC2 will prevent its expression. Allele Variations in OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. The iris consists of five cell layers, the anterior border layer, stroma, the sphincter and dilator muscles fibers, and the posterior pigment epithelium ( Figure 1 ), of which the most important for the appearance of eye colour are the anterior layer and its underlying stroma ( Eagle, 1988; Imesch et al., 1996; Wilkerson et al., 1996 ). Montserrat Rabago-Smith. In contrast, between-population comparisons show good concordance; populations with darker average iris color also tend to exhibit darker average skin tones and hair colors. Google Scholar. For example, OCA2, AIM, DCT, and TYRP1 harbored haplotypes both positively associated with blue irises and negatively associated with brown irises (OCA2 haplotypes 1, 37, 38, 42; AIM haplotype 1; DCT haplotype 2; and TYRP1 haplotype 1; Table 3). Forensic Sci Int: Genet. BLAST searches confirmed the specificity of all primers used. It was unclear from the outset whether we would have better success considering iris color in terms of four colors (blue, green, hazel, and brown) or in terms of groups of colors. OCA2 associations were by far the most significant of any gene or region we tested, while MYO5A SNPs were only weakly associated (but haplotypes and diplotypes more strongly). Accessibility StatementFor more information contact us atinfo@libretexts.orgor check out our status page at https://status.libretexts.org. Hum Mutat 13, 99115 (1999). Abbott C, Jackson I J, Carritt B, Povey S. Akey J M, Wang H, Xiong M, Wu H, Liu W et al. .. Gardner J M, Nakatsu Y, Gondo Y, Lee S, Lyon M F et al. Melanopsin signalling in mammalian iris and retina | Nature In the presence of cysteine, the reaction will proceed to form pheomelanin. E_ Free earlobes. By analyzing the DNA from a crime scene, the general phenotypic traits of the suspect may be pieced together.21, 22, 23 Tully suggests that it may help eliminate particular groups of suspects in circumstances with few leads. Tyrosinase (TYR), the enzyme responsible for pigment production in the body, starts the synthesis of both types of melanin by catalyzing a reaction between tyrosine and dopa, forming dopaquinone. Melanin undergoes a packaging process and if large amounts of P protein are not available to process and transport it, the quality of the darker pigment is compromised and lighter shades will result.14 Demonstrating epistasis, the HERC2 gene affects the results produced by the OCA2 gene. The strongest associations were observed for genes with SNPs that were marginally associated (Table 2) and most of the genes with marginal SNP associations had haplotypes and diplotypes (sometimes referred to as multilocus gene-wise genotypes or diploid pairs of haplotypes) positively (agonist) or negatively (antagonist) associated with at least one iris color (Table 3). pigmented iris genotype - Flix Houphout-Boigny Foundation for Peace The most strongly associated of the marginally associated SNPs were from the OCA2, TYRP1, and AIM genes, in order of the strength of association, which is the same order as that provided using the number of marginally associated SNPs, rather than their strength. You are using a browser version with limited support for CSS. Article To determine the extent to which extant iris color variation could be explained by various models, we calculated R2 values for SNPs, haplotypes, and multilocus genotype data by first assigning the phenotypic value for blue eye color as 1, green eye color as 2, hazel eye color as 3, and brown eye color as 4. Cell Mol Life Sci 62, 18261838 (2005). (2000) with adjusted residuals to compensate for this risk. Duffy, D. L., Montgomery, G. W., Chen, W., Zhao, Z., Le, L., James, M. R. et al. Digital quantification of human eye color highlights genetic association of three new loci. Brilliant, M. The mouse p (pink-eyed dilution) and human P genes, ocular albinism type 2 (OCA2), and melanosomal pH. b) Give the genotype of an individual who is homozygous recessive for brown eye color. .. Shriver M, Parra E, Dios S, Bonilla C, Norton H et al. Article .. Lindsey J D, Jones H L, Hewitt E G, Angert M, Weinreb R N. Lyon M F, King T R, Gondo Y, Gardner J M, Nakatsu Y et al. Garcia-Gonzalo, F. R. & Rosa, J. L. The HERC proteins: functional and evolutionary insights. Albinism - EyeWiki In the rest of the body, the melanin is secreted from the cells. Different SNPs on these two genes were investigated and analyzed for melanoma risk.24, 25. .. Ooi C E, Moreira J E, DellAngelica E C, Poy G, Wassarman D A et al. The decreased expression could account for incomplete dominance, as well. Sequences of the highest order of complexity within a locus found to be associated with iris colors. We will explore some of these single gene traits in the laboratory. Incomplete dominance shows in individuals with lighter shades of brown and hazel. Jannot, A- S., Meziani, R., Bertrand, G., Gerard, B., Descamps, V., Archibaud, A. et al. (2000). 20, 327332 (2004). .. Kanetsky P, Swoyer J, Panossian S, Holmes R, Guerry D et al. Solved In albinism (a recessive disorder), the formation of | Chegg.com This same phenomenon is the reason why the pupil appears black. The disorder is characterized by different-colored irises or different colors within the iris. From a screen of 754 SNP loci, we have identified 61 that are statistically associated with variable iris pigmentation at one level of intragenic complexity or another. Haplotype order refers to the order of the SNPs in the haplotypes shown in Table 4 and described in the text. The large HERC2 gene requires 211kb and 93 exons that codes for a 528kDa protein made of 4834 residues.12. & Driscoll, D. J. Prader-Willi syndrome. Slider with three articles shown per slide. (a) List all possible genotypes for an individual with pigmented iris and dimpled chin. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. We identified numerous SNPs, haplotypes, and diplotypes (diploid pairs of haplotypes) within the OCA2, MYO5A, TYRP1, AIM, DCT, and TYR genes and the CYP1A2-15q22-ter, CYP1B1-2p21, CYP2C8-10q23, CYP2C9-10q24, and MAOA-Xp11.4 regions as significantly associated with iris colors. Within the melanosomes, the tyrosinase (TYR) gene product catalyzes the rate-limiting hydroxylation of tyrosine to 3, 4-dihydroxyphenylanine (DOPA), and the resulting product is oxidized to DOPAquinone to form the precursor for eumelanin synthesis. Linkage disequilibrium (LD) for pairs of SNPs within a gene was determined using the Zaykin exact test and a cutoff value of |D| 0.05 (P value < 0.05; Zaykin et al. Am J Hum Genet 47, 149155 (1990). Blue is confined mostly to people who originated from Europe.11 Green eyes permeate the lowest amount of the population (excluding the disorders), probably due to the lack of coding for it within the genome. Kayser, M., Liu, F., Janssens, A. C., Rivadeneira, F., Lao, O., van Duijn, K. et al. Nonetheless, the study of human OCA mutants suggests that the number of highly penetrant phenotypically active pigmentation loci is surprisingly small. Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K. et al. Although our results independently verified findings for OCA2, ASIP, and MC1R, they also show that several other pigmentation genes harbor alleles associated with the natural distribution of iris colors (TYRP1, AIM, MYO5A, and DCT). OCA2 codes for a major transmembrane protein in the melanosome maturation process: P protein. Pigmented iris: If a person is homozygous recessive for eye color, there is no pigment in the front part of the eyes, and the blue color of the back of the iris shows through, giving blue eyes . When a pigment is deposited in the front layer of the iris, this masks the blue layer to varying degrees. Before the revelation of the effect of HERC2, rs1800407 in exon nine was thought to be the main factor for eye color. Heterochromia, although not viewed as a severe disorder, affects many individuals. In melanocyte-specific organelles known as melanosomes, two pathways for melanogenesis occur. Use a lab partner to help you determine your phenotype for the traits listed. Google Scholar. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. PHRED-qualified sequences were imported into the CLUSTAL X alignment program and the output of this was used with a second program that we developed (T. Frudakis, M. Thomas, Z. Gaskin, K. Venkateswarlu, K. Suresh Chandra, S. Ginjupalli, S. Gunturi, S. Natrajan, V. K. Ponnuswamy and K. N. Ponnuswamy, unpublished results) to identify quality-validated discrepancies between sequences. Edridge Green Lecture RCOphth Annual Congress Glasgow May 2019, A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia, A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness, A large Canadian cohort provides insights into the genetic architecture of human hair colour, Environment and culture shape both the colour lexicon and the genetics of colour perception, A systematic review of skin ageing genes: gene pleiotropy and genes on the chromosomal band 16q24.3 may drive skin ageing, White matter variability, cognition, and disorders: a systematic review, Quantitative changes in iris vasculature and blood flow in patients with different refractive errors, The Effect of Ambient Light Conditions on Quantitative Pupillometry, Functional and pathological relevance of HERC family proteins: a decade later. Google Scholar. id List the possible genotypes of a blue eyed, dimple chinned individual. Molecular and General Genet. Google Scholar. From the chi-square and adjusted residuals, we found 43 haplotypes for 16 different loci to be either positively (agonist) or negatively (antagonist) associated with iris colors (Table 3). Lack of HWE is usually an indication of a poorly designed genotyping assay, but none of the remaining 7 SNPs exhibited genotyping patterns that we have previously associated with such problems (such as the complete absence of an expected genotype class or all genotypes registering as heterozygotes). However, this result would not have necessarily been obtained were we working with SNPs that were not truly associated with iris colors. Internet Explorer). Nine were not and of these 2 were of relatively low frequency with weak evidence for disquilibrium (P value close to 0.05). Science 257, 1121 (1992). 11. Although corrections for multiple testing left most of the SNP-level associations intact, a number of the associations we found did not pass the multiple-testing examination, but nonetheless we present them here to avoid possible type II error; the sequences may be weakly associated with iris colors and possibly relevant within a multiple-gene model for classification (i.e., epistasis). Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. Solved P>p Trait Genotype Phenotypic Effect Relationship P. | Chegg.com Thank you for visiting nature.com. Genotype. Traits.html - Rowan University 1997). Although cysteine is not an essential amino acid and its deficiency rarely occurs, the lack of it halts the production of pheomelanin. This epistatic relationship demonstrates the significance of introns and how a single-base change greatly affects an aspect of the individual. Alternatively, the mechanism for the associations could be LD with phenotypically active loci in nearby pigment genes. Genotyping was performed for individual DNA specimens using a single base primer extension protocol and an SNPstream 25K/ultra-high throughput (UHT) instrument (Beckman Coulter, Fullerton, CA, and Orchid Biosystems, Princeton, NJ). Now, that color depends on the kind and density of melanin a person is born with. In addition, we independently isolated the red hair/blue iris SNP alleles described by Valverde et al. A battery of genetic tests, of which one for the inference of iris color could be a part, could enable the construction of a more objective and science-based (partial) physical profile from crime-scene DNA, and an investigator using these tests would be less interested in the biological mechanism of the phenotype than in an ability to make an accurate inference of trait value. a) Give the genotype of an individual, who is homozygous dominant for Brown eye color, where "B" is the letter used to distinguish this trait. These genes are of the greatest importance for eye color.9, 10, 11, Numerous ubiquitin ligases are coded for throughout the body. The range in eye color, from blue to hazel to brown (see figure one), depends on the level of melanin pigment stored in the melanosome "packets" in the melanocytes of the iris. Once the pigment is produced, MC1R, membrane-associated transporter protein, and p proteins (OCA2) mature the melanosomes to be used in the cells. Predicting phenotype from genotype: normal pigmentation. Indeed, some, but not all, of our nonpigment gene SNPs are found in regions within the vicinity of pigmentation genes; CYP2C8 and CYP2C9 are located on chromosome 10 near the HPS1 and HPS2 pigmentation genes (which we did not test directly), CYP1A2 is located at 15q22ter on the same arm as OCA2 and MYO5A, CYP1B1 is located at 2p21 in the vicinity of the POMC gene at 2p23, and MAOA is located on the same arm of chromosome X (Xp11.411.3) as the OA1 pigmentation gene (which we also did not test directly). Box N F, Duffy D L, Irving R E, Russell A, Chen W et al. ), Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur, Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects, Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans, Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family, Molecular basis of mouse Himalayan mutation, A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12, Molecular structure and chromosomal mapping of the human homolog of the agouti gene, Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2), Induction of tyrosinase gene transcription in human iris organ cultures exposed to latanoprost, Not just pretty eyes: Drosophila eye-colour mutations and lysosomal delivery, Genetic and molecular analysis of recessive alleles at the pink-eyed dilution (p) locus of the mouse, Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4, Mutations within the promoter region of the tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. 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