Once the pigment is produced, MC1R, membrane-associated transporter protein, and p proteins (OCA2) mature the melanosomes to be used in the cells. Indeed, one of those for which the evidence of lack of HWE was the strongest was validated as a legitimate SNP through direct DNA sequencing (data not shown). .. Gardner J M, Nakatsu Y, Gondo Y, Lee S, Lyon M F et al. Valenzuela, R., Henderson, M., Walsh, M., Garrison, N., Kelch, J., Cohen-Barak, O. et al. Other very minor genes are responsible for eye color production, such as agouti signaling protein, but they usually have miniscule effects.5, Finally, two major genes are responsible for eye color: HERC2 and OCA2. 2001). More than likely, their offspring would have blue eyes, but a 25% chance stands that offspring would have brown eyes. Use two alleles per trait for the genotype. However, it is yet to be completely understood. (82%) were in pigmentation genes. We did not confine this higher-order analysis to those genes with marginal SNP associations, but we grouped all of the high-frequency SNPs tested for each gene. Although cysteine is not an essential amino acid and its deficiency rarely occurs, the lack of it halts the production of pheomelanin. Branicki, W., Brudnik, U. In the meantime, to ensure continued support, we are displaying the site without styles Genetic traits - University of Northern Iowa Gene 277, 4962 (2001). Albinism - EyeWiki .. Robbins L S, Nadeau J H, Johnson K R, Kelly M A, Roselli-Rehfuss L et al. The P values we obtained for this particular SNP association (P = 0.010.05, depending on the color criteria) were less significant than those described (P = 0.002) by Rebbeck et al. Peripheral scalloping of the posterior pigmented iris layer. Rather, it seems likely that the structure behind our results is of a finer, more cryptic nature, such as ethnicity or even within-ethnic-group structure. The process that produces melanin, known as melanogenesis, requires numerous proteins. 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. Aside from HERC2 and OCA2, the other genes involved in melanin production have some regions that correlate to other eye colors.5 MC1R contains regions that increase the probability of obtaining green eyes. 5.01 In an experiment designed to study the inheritance of flower color in four-o'clocks, two plants with pink flowers were crossed. Only about half of the 61 SNPs that we identified were associated with iris colors independentlythe others were associated only in the context of haplotypes or diplotypes. 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. For people with brown eyes, some of the cells also have brown pigment in them. The traits that are expressed make up your "phenotype" The allele that is not expressed is the "recessive" allele Forensic Sci Int: Genet. Since most of the SNPs identified from this approach localized to discrete genes or chromosomal regions, we grouped all of the SNPs from each locus and tested inferred haplotypes for association with iris colors using contingency analysis. ISSN 1435-232X (online) .. Bito L Z, Matheny A, Cruickshanks K J, Nondahl D M, Carino O B. Boissy R E, Zhao H, Oetting W S, Austin L M, Wildenberg S C et al. The structure behind our results is unlikely to be of a crude (i.e., continental) nature; although two-thirds of our European-American samples were of significant (4%) BGA admixture, few correlations between structure measured on this level and iris colors were observed in this study. The sequences for most of these genes vary significantly as a function of population structure (Frudakis et al. Amplification products were subcloned into the pTOPO (Invitrogen, San Diego) sequencing vector and 96 insert-positive colonies were grown for plasmid DNA isolation (the use of 670 individuals for the amplification step reduced the likelihood of an individual contributing more than once to this subset of 96 selected). Genotypes for these 754 candidate SNPs were scored for 851 European-derived individuals of self-reported iris colors (292 blue, 100 green, 186 hazel, and 273 brown). In the progeny from this cross, there were 42 plants with red flowers, 86 with pink flowers, and 39 with white flowers. Predicting phenotype from genotype: normal pigmentation. However, a number of the associations we identified were for SNPs located in other types of genes. Rinchik, E. M., Bultman, S. J., Horsthemke, B., Lee, S., Strunk, K. M., Spritz, R. A. et al. 1998; Flanagan et al. 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). Trace your probable genotype from trait 1 through trait 5 until you . The SNP, rs12913832, causes a phenotype change from brown to blue eyes, respectively. There is a useful convention for determining possible gamete genotypesproduced during meiosis from a given parental genotype. How do we get our eye color? | Popular Science and JavaScript. Jannot, A- S., Meziani, R., Bertrand, G., Gerard, B., Descamps, V., Archibaud, A. et al. When there is too little pigment to produce a strong blue color, the red reflections interact with the small amount of blue, producing a violet color.3, The biological process for producing melanin, melanogenesis, involves numerous protein interactions. 1995). B_ genotype for the phenotype of brown eyes (dash indicates second allele could be B or b which means a genotype of BB or Bb) Sturm, R., Duffy, D., Zhao, Z., Leite, F., Stark, M., Hayward, N. et al. 2001). Solved P>p Trait Genotype Phenotypic Effect Relationship P. | Chegg.com Before the revelation of the effect of HERC2, rs1800407 in exon nine was thought to be the main factor for eye color. Although research on pigment mutants has made clear that a small subset of genes is largely responsible for catastrophic pigmentation defects in mice and humans, it remains unclear whether or how common single-nucleotide polymorphisms (SNPs) in these genes contribute toward (or are linked to) natural variation in human iris color. (2002). (Abstr. Attached earlobes. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. The density of granules appears to reach genetically determined levels by early childhood and usually remains constant throughout later life, although a small minority of individuals exhibit changes in color during later stages of life (Bito et al. With the help of dopachrome tautomerase and TYR-related protein 1, eumelanin, the darker pigment, is synthesized; with cysteine, pheomelanin, a yellow-red pigment, is produced. Each of these genes is part of the main (TYR) human pigmentation pathway. Article Box N F, Wyeth J R, OGorman L E, Martin N G, Sturm R A. The OCA2 gene also contains numerous regions for eye color expression. 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. Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. Gardner, J., Nakatsu, Y., Gondo, Y., Lee, S., Lyon, M., King, R. et al. Corresponding author: DNAPrint Genomics, 900 Cocoanut Ave., Sarasota, FL 34236. Sturm, R. A., Teasdale, R. D. & Box, N. F. Human pigmentation genes: identification, structure and consequences of polymorphic variation. 39, 14431452 (2007). Linkage studies have implicated certain pigmentation genes as specifically relevant for pigmentation phenotypes, and most of the pigmentation gene SNPs that we identified clustered to certain genes such as OCA2, MYO5A, TYRP1, and AIM. Although TYR is centrally important for this process, pigmentation in animals is not simply a Mendelian function of TYR or of any other single protein product or gene sequence. To an investigator interested in elucidating a biological mechanism, association due to population structure might not seem to be very satisfying, but when classification is the goal rather than the elucidation of a biological mechanism, it would seem to matter little why a marker is associated with a trait. A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. 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. When light passes through a large amount of melanin, most of the visible light is absorbed, and the little that is reflected back appears brown. Iris phenotypes and pigment dispersion caused by genes influencing Sequences of the highest order of complexity within a locus found to be associated with iris colors. Eye color phenotypes demonstrate both epistasis and incomplete dominance. Am J Hum Genet 47, 149155 (1990). Eye colors are green, hazel, brown or black. Genetic determinants of hair, eye and skin pigmentation in Europeans. However, this result would not have necessarily been obtained were we working with SNPs that were not truly associated with iris colors. Digital quantification of human eye color highlights genetic association of three new loci. To determine whether and how common polymorphisms are associated with natural distributions of iris colors, we surveyed 851 individuals of mainly European descent at 335 SNP loci in 13 pigmentation genes and 419 other SNPs distributed throughout the genome and known or thought to be informative for certain elements of population structure. Tony Frudakis, Matthew Thomas, Zach Gaskin, K Venkateswarlu, K Suresh Chandra, Siva Ginjupalli, Sitaram Gunturi, Sivamani Natrajan, Viswanathan K Ponnuswamy, K N Ponnuswamy, Sequences Associated With Human Iris Pigmentation, Genetics, Volume 165, Issue 4, 1 December 2003, Pages 20712083, https://doi.org/10.1093/genetics/165.4.2071. Each chromosome contains thousands of individual genes. Multiple SNPs were identified on chromosome 10q; the CYP2C8-10p23 region had 1 marginally associated SNP, and the neighboring region, CYP2C9-10p24, also had one. Therefore, it seems that our findings indicate that most of the previous results associating pigmentation gene alleles with iris colors, taken independently, represent merely strokes of a larger, more complex portrait. Green eyes require more pigment than blue and not much less than brown, and because the shades of hazel (brown with blue or green) are more versatile, hazel is still more popular than green. pigmented iris genotype On the HERC2/OCA2 A/A and A/G genotype background there was an increasing proportion of blue eye colour when carrying the IRF4 T allele (P = 3 10-4 ) and a higher number of iris pigmented lesions with the IRF4 T/T homozygote (P = 3 10-9 ). Human pigmentation genes break out into several biochemical pathways, including those for tyrosinase enzyme complex formation on the inner surface of the melanosome, hormonal and environmental regulation, melanoblast migration and differentiation, the intracellular routing of new proteins into the melanosome, and the proper transportation of the melanosomes from the body of the cell into the dendritic arms toward the keratinocytes. Place the PTC paper on your tongue for a few seconds. .. 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 . Biogeographical ancestry admixture proportions were determined using the methods of Hanis et al. For these genes we performed resequencing and of the genes discussed in this article, 113 SNPs were discovered in CYP1A2 (7 gene regions, 5 amplicons, 10 SNPs found), CYP2C8 (9 gene regions, 8 amplicons, 15 SNPs found), CYP2C9 (9 gene regions, 8 amplicons, 24 SNPs found), OCA2 (16 gene regions, 15 amplicons, 40 SNPs found), TYR (5 gene regions, 5 amplicons, 10 SNPs found), and TYRP1 (7 gene regions, 6 amplicons, 14 SNPs found). 2) although some associations were found within nonpigmentation genes such as CYP2C8 at 10q23, CYP2C9 at 10q24, CYP1B1 at 2p21, and MAOA at Xp11.3. The promoter region for OCA2 is located within the HERC2 gene. 1997; Lloyd et al. Hum Genet 123, 177187 (2008). Google Scholar. Donors checked a box for blue, green, hazel, brown, black, or unknown/not clear iris colors, and each had the opportunity to identify whether iris color had changed over the course of their lives or whether the color of each iris was different. Sequences Associated With Human Iris Pigmentation bb genotype for the phenotype of blue eyes. Annals of Hum Genet 73, 160170 (2009). For these subjects, we obtained digital photographs of the right iris, where subjects peered into a box at one end at the camera at the other end to standardize lighting conditions and distance and from which a judge assigned the sample to a color group. 1995; Koppula et al. Provided by the Springer Nature SharedIt content-sharing initiative, Graefe's Archive for Clinical and Experimental Ophthalmology (2022), Cellular and Molecular Life Sciences (2016), Journal of Human Genetics (J Hum Genet) Incomplete dominance shows in individuals with lighter shades of brown and hazel. Frequency of the minor allele and the major and minor allele nucleotide. In the population sample, we were also able to examine the correlation between genotype at the W locus and iris color . Given that our iris color data were self-reported, partitioning the sample into brown and not brown, or blue and not blue, could provide greater power to detect significant associations, particularly for alleles associated with blue or brown irises. Article This information revealed more factors for determining eye color in European populations.20 Tully, Valenzuela and Zaumseger suggest using genotype data for forensic analysis. The front layer of the iris (called the stroma) can make eyes appear brown, blue or green. Google Scholar. Eye color results from varying degrees of melanin produced in the melanocytes of the iris. 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). Iris transillumination: The iris in albinism has little to no pigment to screen out stray light coming into the eye.On slit lamp exam, the examiner may detect speckled or diffuse transillumination defect. Pathway I contains gene A that produces an enzyme to catalyze conversion of a colorless pigment designated white1 to blue pigment. .. Lee S-T, Nicholls R D, Schnur R E, Guida L C, Lu-Kuo J et al. In the presence of cysteine, the reaction will proceed to form pheomelanin. brown, hazel) pp Blue Iris (non-pigmented) PG-1: In a human population exhibiting Hardy-Weinberg Equilibrium for the eye pigmentation gene, 81% of the people have blue (non-pigmented) irises. . Childhood glaucoma | Ento Key 1997). 2002). What is the likely genotype of individual C-4? The traditional view was correct in which an allele that codes for brown is dominant over green or blue, and green takes precedence over blue.2, Melanocytes in the stroma and anterior layers of the eye hold melanin in their cytoplasms. Similar to a lack of TYR, other conditions cause ocular albinism. 1993; Smith et al. 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). record your observations. White, D., Rabago-Smith, M. Genotypephenotype associations and human eye color. 1998; Schioth et al. 1991; Boissy et al. We developed a program (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 design resequencing primers in a manner respectful of homologous sequences in the genome, to ensure that we did not coamplify pseudogenes or amplify from within repeats. Eye color genes. Google Scholar. Human Genetics: Simple inheritance - Antranik However, single-gene studies have not provided a sound basis for understanding the complex genetics of human iris color. .. Rebbeck T R, Kanetsky P A, Walker A H, Holmes R, Halpern A C et al. Eye color ranges include varying shades of brown, hazel, green, blue, gray, and in rare cases, violet and red. PTC tasting If you can taste PTC, you have the dominant allele (P). Montserrat Rabago-Smith. Genotypes were subject to several quality controls: two scientists independently pass/fail inspected the calls, requiring an overall UHT signal intensity >1000 for >95% of genotypes and clear signal differential between the averages for each genotype class (i.e., clear genotype clustering in two-dimensional space using the UHT analysis software). Solved Chapter 1: Heredity and the back of the Iris shows | Chegg.com It is toward this goal that we have performed the present study. .. Steenland K, Bray I, Greenland S, Boffetta P. Strobel M C, Seperack P K, Copeland N G, Jenkins N A. Valverde P, Healy E, Jackson I, Rees J L, Thody A J. Wilson S M, Yip R, Swing D A, OSullivan T N, Zhang Y et al. Accessibility StatementFor more information contact us atinfo@libretexts.orgor check out our status page at https://status.libretexts.org. Petunias with genotype R1R1 are red flowered, R1R2 are pink flowered and R2R2 are white flowered. Further, certain of our results support the previous literature. In the absence of melanin brown pigment, the iris is blue. Frudakis, T., Thomas, M., Gaskin, Z., Venkateswarlu, K., Chandra, K. S., Ginjupalli, S. et al. The disorder is characterized by different-colored irises or different colors within the iris. Refer to TABLE II. For each gene, we inferred haplotypes and used contingency analyses to determine which haplotypes were statistically associated with iris colors. as a function of BGA (Frudakis et al. PLoS Genet 6, e1000934 (2010). Multiple SNPs were also identified on chromosome 2; the C/C genotype for the POMC SNP located at 2p23 was associated with blue iris color (Table 3) and a CYP1B1-2p21-region SNP was also marginally associated at the level of iris shade (Table 2), as well as within the context of a 2-SNP haplotype (Table 3). When a T is replaced with a C in rs12913832 of intron 86, OCA2 transcription is depressed, resulting in a blue-eyed individual. 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. & Driscoll, D. J. Prader-Willi syndrome. Pigmented iris A person with the B allele has brown eyes. Oetting, W. S. & King, R. A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Finally, in addition to the OCA2 (15q11.2q12) and MYO5A (15q21) sequences, a single SNP (15q22ter) was also implicated on chromosome 15q, but SNPs between each of these three loci were not found to be in LD (data not shown). Diplotypes for these 61 alleles explained most of the iris color variance in our sample; the lowest amount was explained at the level of the SNP, suggesting an element of intragenic complexity to iris color determination (i.e., dominance). For those remaining, only a single round of PCR was performed. We sincerely thank the referees for their valuable suggestions for improvements on the earlier version of this article. Solved Trait Genotype Phenotypic | Chegg.com Cell Mol Life Sci 62, 18261838 (2005). Pigmented irises. In the most elementary form, the inheritance of eye color is classified as a Mendelian trait.1 On the basis of the observation of more than two phenotypes, eye color has a more complex pattern of inheritance. Sequences associated with human iris pigmentation. 1997; Smith et al. Although we screened a large number of SNPs, some of the genes harbor a large number of candidate SNPs and we did not test them all. b) Give the genotype of an individual who is homozygous recessive for brown eye color. This is an example of a hihybrid crosses. Since most individuals of non-European or minority European descent exhibit low variability in iris colors (on average of darker shade than individuals of European descent), this improvement may not seem surprising. Twin Res 7, 197210 (2004). 2003; data not shown). _____ Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. 1999; Flanagan et al. However, the results presented herein constitute a good first step toward solving what our results confirm is a very complex genetics problem. Blue Iris (non-pigmented) MG-3: Jeremy has attached earlobes and pigmented irises. Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K. et al. If no haplotypes or diplotypes for a locus were found to be associated, only the SNP alleles are shown. This same phenomenon is the reason why the pupil appears black. A brown-iris locus was localized to an interval containing the OCA2 and MYO5A genes (Eiberg and Mohr 1996), and specific polymorphisms in the MC1R gene have been shown to be associated with red hair and blue iris color in relatively isolated populations (Robbins et al. Although this could indicate that the SNPs are in LD with other phenotypically active loci, it may also be a reflection that variability in message transcription and/or turnover may explain part of the variability observed in human iris colors. The rest were found in or around xenobiotic metabolism genes, which we have previously shown exhibit dramatic sequence variation, Candidate genes tested for sequence associations with human iris pigmentation. However, it is yet to be completely understood. .. 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. CAS 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. 20, 327332 (2004). 1991; Chintamaneni et al. All of the major sequences (count 13) for each locus with at least one significantly associated sequence are shown. The large HERC2 gene requires 211kb and 93 exons that codes for a 528kDa protein made of 4834 residues.12. Although such an error is tolerable for identifying sequences marginally associated with iris colors, the use of the sequences described herein for iris color classification would therefore likely require digitally quantified iris colors (which we have begun to accumulate and will present elsewhere). 2001) and that disparate regions of the TYR and other OCA genes are functionally distinct for determining the pigmentation in different tissues. 2000). .. Kwon H Y, Bultman S J, Loffler C, Chen W-J, Furdon P J et al. BLAST searches confirmed the specificity of all primers used. These two seemingly unrelated genes have a major effect on eye color in humans. What is your genotype for this trait? In fact, study of the transmission genetics for pigmentation traits in humans and various model systems suggests that variable pigmentation is a function of multiple heritable factors whose interactions appear to be quite complex (Brauer and Chopra 1978; Bito et al. The exact nature and density If you exhibit the dominant phenotype, use a dash to represent the second allele. Legal. The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman Syndromes. European J Genet 17, 317 (2009). 2000), and adaptin 3B (AP3B) loci (Ooi et al. A change in rs1800407 causes a change in the protein, Arg419Gln, and a change from brown to blue eyes. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The first step, however, is to define the complement of loci that on a sequence level explain variance in trait value and, of these, those that do so in a marginal or penetrant sense will be the easiest to find. Redei, G. Encyclopedia of Genetics, Genomics, Proteomics, and Informatics, 3rd edn (Springer, New York City, NY, 2008). Apart from representing the first comprehensive candidate gene study for variable iris pigmentation and constituting a first step toward developing a classification model for the inference of iris color from DNA, our results suggest that cryptic population structure might serve as a leverage tool for complex trait gene mapping if genomes are screened with the appropriate ancestry informative markers. His wife Jenny has free earlobes and . Collin College Faculty Web Directory European J Hum Genet 13, 913920 (2005). Already, some researchers have started studying hues and saturations. 1997). Supplement Series 1, 544546 (2008). In addition, for 103 of the subjects, iris colors were reported using a number from 1 to 11 as well, where 1 is the darkest brown/black and 11 is the lightest blue, identified using a color placard. The quantity and quality of melanin in the cytoplasm determines the observed color of the eye. These analyses resulted in the identification of 61 SNPs in 16 genes/chromosomal regions associated with iris colors on one level or another; details for each and whether the SNP is marginally associated or associated within the context of the haplotype and/or diplotype are shown in Table 2. 11. They help with hormone secretion, which affects the pituitary and can lead to dysfunction of the hypothalamus and other protein complexes. This finding, while common with albinism, is not specific as iris transillumination occurs in diseases unrelated to albinism such as pseudoexfoliation, pigment dispersion syndrome . Depending on how little pigment the melanocytes produce, albinism causes red or violet eyes. (2002) recently described two OCA2 coding changes associated with darker iris colors. 1997, 2001; Akey et al. Melanocortin 1 receptor (MC1R) instructs a melanocyte to switch production between eumelanin and pheomelanin.3, 4, 5 Therefore, these two proteins affect the quality and quantity of the melanin in the cell. Before screening these genotypes for association with iris colors, we used the 73 nonxenobiotic metabolism AIMs to determine BGA admixture proportions for each sample and we tested for correlation between BGA admixture and iris colors. For these, it would seem more prudent to eliminate false positives downstream of SNP identification, such as from tests of higher-order association, using various other criteria, such as those described above, or possibly using the utility of the SNP for the generalization of a complex classification model when one is finally described. .. Shriver M, Parra E, Dios S, Bonilla C, Norton H et al. TYR catalyzes the rate-limiting step of melanin biosynthesis and the degree to which human irises are pigmented correlates well with the amplitude of TYR message levels (Lindsey et al. (2001) haplotype reconstruction method. .. Ooi C E, Moreira J E, DellAngelica E C, Poy G, Wassarman D A et al. Cassidy, S. B. 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. The colored area at the front of the eye is called the iris. 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.
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