利用兄弟數據之多點遺傳連鎖分析方法

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王紋璋(Wen-Chang Wang) 查詢紙本館藏

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數學系

論文名稱

利用兄弟數據之多點遺傳連鎖分析方法
(A Monte Carlo Method for Linkage Analysis with Sibship Genotype Data)

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摘要(英)

We propose a new Monte Carlo approach to the problem of calculating the conditional
probability of inheritance patterns given sibship genotype data in multipoint linkage analysis.
By limiting the study to sibships, we hope to have a linkage analysis method that can
incorporate general crossover process model and can be used to examine the issue of genetic
interference in the context of linkage studies. This thesis is separated into three parts.
In Part I, we introduce the new Monte Carlo approach of multipoint linkage analysis. Our
approach is mainly an application of importance sampling method. The crossover distribution
used in this approach is estimated from the CEPH and Icelandic family genotype data.
Estimation of this crossover distribution is described in Part III. To make the computation
efficient, we show that the calculation of the probability of legal ordered parental genotype
given sibship genotype and inheritance patterns can be carried out quickly by a
straight-forward classification of inheritance patterns. To evaluate the performance of our
method, we compare the performance of our method with that of GENEHUNTER in terms of
the accuracy in calculating the conditional probability of IBD sharing for sib-pairs in CEPH
families given the sibship genotype on chromosome 19.
In Part II, we deal with the set of legal inheritance vectors for a sibship at one marker. We
classify the sibships according to the genotype of the sibs into 9 classes, and list explicitly the
set of legal inheritance vectors for each class. Because an inheritance pattern is legal at
several markers if it is legal at everyone of these markers, results in Part II can be extended
directly to the set of legal inheritance patterns for many markers. We use the result to reduce
the time and memory needed in our Monte Carlo approach in Part I.
In Part III, we provide a nonparametric estimate of the crossover distribution on the basis
of the CEPH family genotype data, the Icelandic family genotype data, and the order of the
markers where genotype data are taken. The only assumption employed in this approach is
that, in one meiosis, there is at most one crossover point between markers close enough to
each other. This estimated crossover distribution can be used in multipoint linkage analysis
without the assumption of no interference.

關鍵字(中)

★ 遺傳連鎖分析
★ 兄弟數據

關鍵字(英)

★ Monte Carlo method
★ multipoint linkage analysis
★ sibship genotype data

論文目次

Part I
A Monte Carlo Method for Linkage Analysis with Sibship Genotype Data
Introduction 2
Material and Methods 5
Calculate P(v,g) 5
Calculate P(g) 7
Calculate Linkage Statistics 8
Results 10
Discussion 12
Appendix 13
References 16
Tables 20
Part II
The Set of Legal Inheritance Vectors for a Sibship
Introduction 23
Material and Methods 24
Appendix 28
References 33
Tables 34
Part III
Nonparametric Estimate of the Distribution of Crossover Points for Meioses in the CEPH and Icelandic Families
Introduction 45
Material and Methods 46
Genotype Data 46
Reconstruction of the Crossover Points 47
Estimation Procedure 50
Results 52
Reconstruction of Crossover Points for Chromosome 19 52
Appendix 53
References 54
Tables 56
Figures 58

參考文獻

Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin-rapid analysis of
dense genetic maps using sparse gene
ow trees. Nat Genet 30:97-101
Broman KW, Murray JC, She eld VC, White RL, Weber JL (1998) Comprehensive
human genetic maps: individual and sex-speci c variation in recombination. Am J
Hum Genet 63:861-869
Broman KW, Weber JL (2000) Characterization of Human Crossover Interference. Am
J Hum Genet 66:1911-1926
Cannings C, Thompson EA, Skolnick MH (1978) Probability functions on complex pedigrees.
Adv Appl Prob 10:26-61
Cottingham RW Jr, Idury RM, Scha er AA (1993) Faster sequential genetic linkage
computations. Am J Hum Genet 53:252-263
Daw EW, Thompson EA, Wijsman EM (2000) Bias in multipoint linkage analysis arising
from map misspeci cation. Genet Epidemiol 19:366-380
Elston RC, Stewart J (1971) A general model for the genetic analysis of pedigree data.
Hum Hered 21:523-542
Geweke J (1989) Bayesian inference in econometric models using Monte Carlo integration.
Econometrica 57:1317-1340
Gretarsdottir S, Sveinbjornsdottir S, Jonsson HH, Jakobsson F, Einarsdottir E, Agnarsson
U, Shkolny D, Einarsson G, Gudjonsdottir HM, Valdimarsson EM, Einarsson
OB, Thorgeirsson G, Hadzic R, Jonsdottir S, Reynisdottir ST, Bjarnadottir SM,
Gudmundsdottir T, Gudlaugsdottir GJ, Gill R, Lindpaintner K, Sainz J, Hannesson
HH, Sigurdsson GT, Frigge ML, Kong A, Gudnason V, Stefansson K, Gulcher
JR (2002) Localization of a susceptibility gene for common forms of stroke to 5q12.
Am J Hum Genet 70:593-603
17
Halpern J, Whittemore AS (1999) Multipoint linkage analysis. Hum Hered 49:194-196
Housworth EA, Stahl FW (2003) Crossover interference in humans. Am J Hum Genet
73:188-197
Idury RM, Elston RC (1997) A faster and more general hidden Markov model algorithm
for multipoint likelihood calculations. Hum Hered 47:197-202
Irwin M, Cox N, Kong A (1994) Sequential imputation for multilocus linkage analysis.
Proc Natl Acad Sci USA 91:11684-11688
Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B,
Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson ST, Frigge
ML, Thorgeirsson TE, Gulcher JR, Stefansson K (2002) A high-resolution recombination
map of the human genome. Nat Genet 31:241-247
Kruglyak L, Daly MJ, Lander ES (1995) Rapid multipoint linkage analysis of recessive
traits in nuclear families, including homozygosity mapping. Am J Hum Genet
56:519-527
Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996) Parametric and nonparametric
linkage analysis: a uni ed multipoint approach. Am J Hum Genet 58:1347-1363
Kruglyak L, Lander ES (1998) Faster multipoint linkage analysis using Fourier transforms.
J Comput Biol 5:1-7
Lander ES, Green P (1987) Construction of multilocus genetic maps in humans. Proc
Natl Acad Sci USA 84:2363-2367
Lange K (2002) Mathematical and Statistical Methods for Genetic Analysis, 2d ed.
Springer, New York.
Lin S, Cheng R, Wright FA (2001) Genetic crossover interference in the human genome.
Ann Hum Genet 65:79-93
18
Lin S, Speed TP (1996) Incorporating crossover interference into pedigree analysis using
the 2 model. Hum Hered 46:315-322
Markianos K, Daly MJ, Kruglyak L (2001) E cient multipoint linkage analysis through
reduction of inheritance space. Am J Hum Genet 68:963-977
Matise TC, Sachidanandam S, Clark AG, Kruglyak L, Wijsman E, Kakol J, Buyske
S, Chui B, Cohen P, Toma C, Ehm M, Glanowski S, He C, Heil J, Markianos K,
McMullen I, Pericak-Vance MA, Silbergleit A, Stein L, Wagner M, Wilson AF,
Winick JD, Winn-Deen ES, Yamashiro CT, Cann HM, Lai E, Holden AL (2003)
A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map
and screening set. Am J Hum Genet 73:271-284
O'Connell JR, Weeks DE (1995) The VITESSE algorithm for rapid exact multilocus
linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet 11:402-
408
Ranade K, Hsuing CA, Wu KD, Chang MS, Chen YT, Hebert J, Chen I, Olshen R, Curb
D, Dzau V, Botstein D, Cox D, Risch N (2000) Lack of evidence for an association
between alpha-adduciun and blood pressure regulation in asian populations. Amer
J Hypertension 13:704-709
Robert CP, Casella G (1999) Monte Carlo Statistical Methods. Springer, New York.
Skrivanek Z, Lin S, Irwin M (2003) Linkage analysis with sequential imputation. Genet
Epidemiol 25:25-35
Sobel E, Lange K (1996) Descent graphs in pedigree analysis: applications to haplotyping,
location scores, and marker-sharing statistics. Am J Hum Genet 58:1323-1337
Thompson EA (2000) Statistical inferences from genetic data on pedigrees. Vol 6.
NSF-CBMS Regional Conference Series in Probability and Statistics, Beachwood,
OH:IMS.
19
Wang WC, Chen WC, Hsiung CA, Chang IS (2003a) Nonparametric estimate of the
distribution of crossover points for meioses in the CEPH and Icelandic families.
(Preprint)
Wang WC, Chuang YC, Chang IS (2003b) The set of legal inheritance vectors for a
sibship. (Preprint)
Weber JL (2002) The Iceland map. Nat Genet 31:1-2
Zhao H, Speed TP, McPeek MS (1995) Statistical Analysis of Crossover Interference
Using the Chi-Square Model. Genetics 139:1045-1056
Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996) Parametric and nonparametric
linkage analysis: a uni ed multipoint approach. Am J Hum Genet 58:1347-1363
Markianos K, Daly MJ, Kruglyak L (2001) E cient multipoint linkage analysis through
reduction of inheritance space. Am J Hum Genet 68:963-977
Sobel E, Lange K (1996) Descent graphs in pedigree analysis: applications to haplotyping,
location scores, and marker-sharing statistics. Am J Hum Genet 58:1323-1337
Wang WC, Chuang YC, Hsiung CA, Chang IS (2003) A Monte Carlo method for linkage
analysis with sibship genotype data. (Preprint)
Broman KW, Murray JC, She eld VC, White RL, Weber JL (1998) Comprehensive
human genetic maps: individual and sex-speci c variation in recombination. Am J
Hum Genet 63:861-869
Dausset J, Cann H, Cohen D, Lathrop M, Lalouel JM, White R (1990) Centre d'etude
du polymorphisme humain (CEPH): collaborative genetic mapping of the human
genome. Genomics 6:575-577
Fisher RA, Lyon MF, Owen ARG (1947) The sex chromosome of the house mouse.
Heredity 1:335-365
Goldgar DE, Fain PR (1988) Models of multilocus recombination: nonrandomness in
chiasma number and crossover positions. Am J Hum Genet 43:38-45
Karlin S, Liberman U (1979) A natural class of multilocus recombination processes and
related measures of crossover interference. Adv Appl Probab 11:479-501
Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B,
Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson ST, Frigge
ML, Thorgeirsson TE, Gulcher JR, Stefansson K (2002) A high-resolution recombination
map of the human genome. Nat Genet 31:241-247
Lamb NE, Feingold E, Sherman SL (1997) Estimating meiotic exchange patterns from
recombination data: an application to humans. Genetics 146:1011-1017
Lander ES, Green P (1987) Construction of multilocus genetic maps in humans. Proc
Natl Acad Sci USA 84:2363-2367
Lange K, Zhao H, Speed TP (1997) The Poisson-skip model of crossing-over. Ann Appl
Probab 7:299-313
Lin S, Speed TP (1996) Incorporating crossover interference into pedigree analysis msing
the 2 model. Hum Hered 46:315-322
55
Risch N, Lange K (1979) An alternative model of recombination and interference. Ann
Hum Genet 43:61-70
Skrivanek Z, Lin S, Irwin M (2003) Linkage analysis with sequential imputation. Genet
Epidemiol 25:25-35
Wang WC, Chuang YC, Hsiung CA, Chang IS (2003) A Monte Carlo method for linkage
analysis with sibship genotype data. (Preprint)
Weber JL (2002) The iceland map. Nat Genet 31:1-2
Weinstein A (1936) The theory of multiple-strand crossing over. Genetics 21:155-199
Zhao H, Speed TP, McPeek MS (1995) Statistical analysis of crossover interference using
the chi-square model. Genetics 139:1045-1056

指導教授

張憶壽、熊昭
(I-Shou Chang、Chao A. Hsiung)

審核日期

2003-12-29

推文