Use of Homozygosity Mapping to Identify a Region on Chromosome 1 Bearing a Defective Gene That Causes Autosomal Recessive Homozygous Hypercholesterolemia.

Slides:

Advertisements

Similar presentations

Copyright © 2001 American Medical Association. All rights reserved.

Advertisements

Autosomal Dominant Postaxial Polydactyly, Nail Dystrophy, and Dental Abnormalities Map to Chromosome 4p16, in the Region Containing the Ellis–van Creveld.

Copyright © 1999 American Medical Association. All rights reserved.

The Gene for Glycogen-Storage Disease Type 1b Maps to Chromosome 11q23

Identification of a Novel Locus Associated with Congenital Recessive Ichthyosis on 12p11.2–q13 Mordechai Mizrachi-Koren, Dan Geiger, Margarita Indelman,

Mapping of a Locus for a Familial Autosomal Recessive Idiopathic Myoclonic Epilepsy of Infancy to Chromosome 16p13 Federico Zara, Elena Gennaro, Mariano.

Genomewide Linkage Analysis Identifies Polymorphism in the Human Interferon-γ Receptor Affecting Helicobacter pylori Infection Thorsten Thye, Gerd D.

Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Adolfo.

Homozygosity Mapping in Families with Joubert Syndrome Identifies a Locus on Chromosome 9q34.3 and Evidence for Genetic Heterogeneity Kathrin Saar, Lihadh.

Genetic Linkage of Paget Disease of the Bone to Chromosome 18q

A Second Locus for Familial Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2q21-q33 Stéphanie Baulac, Isabelle Gourfinkel-An, Fabienne.

D. E. Grice, K. A. Halmi, M. M. Fichter, M. Strober, D. B. Woodside, J

Genomewide Scan in German Families Reveals Evidence for a Novel Psoriasis- Susceptibility Locus on Chromosome 19p13 Young-Ae Lee, Franz Rüschendorf, Christine.

Soraya Beiraghi, Swapan K. Nath, Matthew Gaines, Desh D

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p Shenghan Chen, William G. Ondo, Shaoqi Rao,

An Autosomal Dominant Thrombocytopenia Gene Maps to Chromosomal Region 10p Anna Savoia, Maria Del Vecchio, Antonio Totaro, Silverio Perrotta, Giovanni.

The SPCH1 Region on Human 7q31: Genomic Characterization of the Critical Interval and Localization of Translocations Associated with Speech and Language.

A Combined Linkage-Physical Map of the Human Genome

The Gene for Glycogen-Storage Disease Type 1b Maps to Chromosome 11q23

Caroline Durrant, Krina T. Zondervan, Lon R

Tamara Rogers, David Chandler, Dora Angelicheva, P. K

Use of Closely Related Affected Individuals for the Genetic Study of Complex Diseases in Founder Populations C. Bourgain, E. Génin, P. Holopainen, K.

The Gene for Severe Combined Immunodeficiency Disease in Athabascan-Speaking Native Americans Is Located on Chromosome 10p Lanying Li, Dennis Drayna,

Lan Xiong, Malgorzata Labuda, Dong-Sheng Li, Thomas J

Evidence for a Nonallelic Heterogeneity of Epidermodysplasia Verruciformis with Two Susceptibility Loci Mapped to Chromosome Regions 2p21–p24 and 17q25

A Second Gene for Autosomal Dominant Möbius Syndrome Is Localized to Chromosome 10q, in a Dutch Family H.T.F.M. Verzijl, B. van den Helm, B. Veldman,

A Third Major Locus for Autosomal Dominant Hypercholesterolemia Maps to 1p34.1- p32 Mathilde Varret, Jean-Pierre Rabès, Bruno Saint-Jore, Ana Cenarro,

Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3– q24.2 Ping Liu, Qingyu Yang, Xu Wang, Aiping Feng, Tao Yang, Rong Yang,

John D. Rioux, Valerie A. Stone, Mark J

Familial Juvenile Hyperuricemic Nephropathy: Localization of the Gene on Chromosome 16p11.2—and Evidence for Genetic Heterogeneity Blanka Stibůrková,

A Gene for Familial Juvenile Polyposis Maps to Chromosome 18q21.1

The Gene for Human Fibronectin Glomerulopathy Maps to 1q32, in the Region of the Regulation of Complement Activation Gene Cluster Martin Vollmer, Martin.

Refinement of the Locus for Autosomal Recessive Retinitis Pigmentosa (RP25) Linked to Chromosome 6q in a Family of Pakistani Origin Shagufta Khaliq,

Airong Li, Sonia Davila, Laszlo Furu, Qi Qian, Xin Tian, Patrick S

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

Genetic and Mutational Analyses of a Large Multiethnic Bardet-Biedl Cohort Reveal a Minor Involvement of BBS6 and Delineate the Critical Intervals of.

Multipoint Approximations of Identity-by-Descent Probabilities for Accurate Linkage Analysis of Distantly Related Individuals Cornelis A. Albers, Jim.

Hal M. Hoffman, Fred A. Wright, David H. Broide, Alan A

Mapping of a Locus for a Familial Autosomal Recessive Idiopathic Myoclonic Epilepsy of Infancy to Chromosome 16p13 Federico Zara, Elena Gennaro, Mariano.

A Locus for Brachydactyly Type A-1 Maps to Chromosome 2q35-q36

Stephen C. Pratt, Mark J. Daly, Leonid Kruglyak

Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31 Binoy Appukuttan, Elizabeth Gillanders, Suh-Hang Juo, Diana Freas-Lutz, Sandra.

Genetic Linkage of Autosomal-Dominant Alport Syndrome with Leukocyte Inclusions and Macrothrombocytopenia (Fechtner Syndrome) to Chromosome 22q11-13

Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12- q12 and Evidence for Further Genetic Heterogeneity Judith Fischer, Alexandra.

D. E. Grice, K. A. Halmi, M. M. Fichter, M. Strober, D. B. Woodside, J

Homozygosity and Linkage-Disequilibrium Mapping of the Syndrome of Congenital Hypoparathyroidism, Growth and Mental Retardation, and Dysmorphism to a.

Retinitis Pigmentosa and Progressive Sensorineural Hearing Loss Caused by a C12258A Mutation in the Mitochondrial MTTS2 Gene Fiona C. Mansergh, Sophia.

A Severely Affected Male Born into a Rett Syndrome Kindred Supports X-Linked Inheritance and Allows Extension of the Exclusion Map Carolyn Schanen, Uta.

Localization of the Fourth Locus (GLC1E) For Adult-Onset Primary Open-Angle Glaucoma to the 10p15-p14 Region Mansoor Sarfarazi, Anne Child, Diliana Stoilova,

Genomewide Scan in Families with Schizophrenia from the Founder Population of Afrikaners Reveals Evidence for Linkage and Uniparental Disomy on Chromosome.

Evidence That the Penetrance of Mutations at the RP11 Locus Causing Dominant Retinitis Pigmentosa Is Influenced by a Gene Linked to the Homologous RP11.

Mapping of Gene Loci for Nephronophthisis Type 4 and Senior-Løken Syndrome, to Chromosome 1p36 Maria J. Schuermann, Edgar Otto, Achim Becker, Katrin.

Localization of a Gene for Autosomal Recessive Distal Renal Tubular Acidosis with Normal Hearing (rdRTA2) to 7q33-34 Fiona E. Karet, Karin E. Finberg,

Genomewide Search and Genetic Localization of a Second Gene Associated with Autosomal Dominant Branchio-Oto-Renal Syndrome: Clinical and Genetic Implications

Hereditary Isolated Renal Magnesium Loss Maps to Chromosome 11q23

A Deletion Mutation in COL17A1 in Five Austrian Families with Generalized Atrophic Benign Epidermolysis Bullosa Represents Propagation of an Ancestral.

A New Locus for Autosomal Recessive Hypercholesterolemia Maps to Human Chromosome 15q25-q26 Milco Ciccarese, Adolfo Pacifico, Giancarlo Tonolo, Paolo.

Identification, by Homozygosity Mapping, of a Novel Locus for Autosomal Recessive Congenital Ichthyosis on Chromosome 17p, and Evidence for Further Genetic.

Amalia Martinez-Mir, Jianjun Liu, Derek Gordon, Madeline S

A Gene for an Autosomal Dominant Scleroatrophic Syndrome Predisposing to Skin Cancer (Huriez Syndrome) Maps to Chromosome 4q23 Young-Ae Lee, Howard P.

Identification of a New Gene Locus for Adolescent Nephronophthisis, on Chromosome 3q22 in a Large Venezuelan Pedigree Heymut Omran, Carmen Fernandez,

Simone Sanna-Cherchi, Gianluca Caridi, Patricia L

A New Familial Amyotrophic Lateral Sclerosis Locus on Chromosome 16q12

Assignment of the Muscle-Eye-Brain Disease Gene to 1p32-p34 by Linkage Analysis and Homozygosity Mapping Bru Cormand, Kristiina Avela, Helena Pihko,

Homozygosity Mapping Places the Acrodermatitis Enteropathica Gene on Chromosomal Region 8q24.3 Kun Wang, Elizabeth W. Pugh, Shari Griffen, Kimberly F.

Homozygosity Mapping in Families with Joubert Syndrome Identifies a Locus on Chromosome 9q34.3 and Evidence for Genetic Heterogeneity Kathrin Saar, Lihadh.

A Locus for Autosomal Dominant Hereditary Spastic Ataxia, SAX1,Maps to Chromosome 12p13 I.A. Meijer, C.K. Hand, K.K. Grewal, M.G. Stefanelli, E.J. Ives,

Genome-wide High-Density SNP-Based Linkage Analysis of Infantile Hypertrophic Pyloric Stenosis Identifies Loci on Chromosomes 11q14-q22 and Xq23 Kate.

Autosomal Recessive Cerebellar Ataxia with Oculomotor Apraxia (Ataxia- Telangiectasia–Like Syndrome) Is Linked to Chromosome 9q34 Andrea H. Németh, Elena.

Linkage of Familial Hemophagocytic Lymphohistiocytosis to 10q21-22 and Evidence for Heterogeneity Rémi Dufourcq-Lagelouse, Nada Jabado, Françoise Le.

Presentation transcript:

Use of Homozygosity Mapping to Identify a Region on Chromosome 1 Bearing a Defective Gene That Causes Autosomal Recessive Homozygous Hypercholesterolemia in Two Unrelated Families Emily R. Eden, Rossitza P. Naoumova, Jemima J. Burden, Mark I. McCarthy, Anne K. Soutar The American Journal of Human Genetics Volume 68, Issue 3, Pages 653-660 (March 2001) DOI: 10.1086/318795 Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigrees of families with autosomal recessive hypercholesterolemia not caused by mutations in the LDL-receptor gene. The pretreatment plasma cholesterol concentration (mM/l) of each individual is indicated below each symbol; the plasma cholesterol level for individual 14 in pedigree 1 was reported to be in the normal range. Symbols enclosing dotted lines indicate affected individuals, and symbols containing numbers indicate individuals who were included in the genetic analysis. Arrows indicate probands. The American Journal of Human Genetics 2001 68, 653-660DOI: (10.1086/318795) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 2 Haplotypes for the region of homozygosity on chromosome 1p36-35. Haplotypes for individuals in pedigrees 1 and 2, with the affected individuals shown as filled symbols, were as constructed by GENEHUNTER (Kruglyak and Lander 1995); the approximate genetic distances between the markers were taken from the Généthon human linkage map (Dib et al. 1996) or from the LDB. Markers accompanied by an asterisk (*) were taken from the LDB and are shown on the left of the markers. Boxes indicate the region of homozygosity in affected individuals. Also indicated is the region on chromosome 1p32 that has been mapped in pedigrees with autosomal dominant hypercholesterolemia (Hunt et al. 2000; Varret el al. 1999). The American Journal of Human Genetics 2001 68, 653-660DOI: (10.1086/318795) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 3 Linkage of the defect to chromosome 1p36-1p35. Parametric LOD scores for linkage on chromosome 1 were determined by GENEHUNTER (Kruglyak and Lander 1995), under an autosomal recessive model of inheritance in which it was assumed that the disease phenotype was 98% penetrant and that the disease-gene frequency was .002. Pedigree 1, solid line; pedigree 2, dashed line. Individuals 15, 16, and 18 in pedigree 1 could not be included because of the constraints of the software. The American Journal of Human Genetics 2001 68, 653-660DOI: (10.1086/318795) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 4 Combined LOD scores obtained in a genomewide screen with polymorphic markers in pedigrees 1 and 2. A genomewide screen, with markers located at ∼8-cM intervals, was performed for the individuals as indicated in figure 1. Combined LOD scores were determined by GENEHUNTER analysis, but individuals 15, 16, and 18 in pedigree 1 could not be included because of the limitations of the software. The linkage analyses were performed under an autosomal recessive model of inheritance in which it was assumed that the disease phenotype was 98% penetrant and that the disease gene frequency was .002. The American Journal of Human Genetics 2001 68, 653-660DOI: (10.1086/318795) Copyright © 2001 The American Society of Human Genetics Terms and Conditions

Figure 5 Exclusion of homozygosity in pedigrees 1 and 2 on chromosome 15q25-q26. Genotyping was performed with markers spanning a region on chromosome 15 that has recently been mapped in Sardinian families with a variant form of inherited autosomal recessive hypercholesterolemia (Ciccarese et al. 2000); the markers that delineate the 16-cM region of linkage on 15q25-q26 in that study are underlined. X indicates recombination events. The American Journal of Human Genetics 2001 68, 653-660DOI: (10.1086/318795) Copyright © 2001 The American Society of Human Genetics Terms and Conditions