COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXIX

COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOG Y

Founded in 1933

by REGINALD G. HARRIS

Director of the Biological Laboratory

1924 to 1936

The Symposia were organized and managed by Dr. Harris until his death. Their continued use- fulness is a tribute to the soundness of his vision.

The Symposium Volumes are published by the Cold Spring Harbor

Laboratory of Quantitative Biology Cold Spring Harbor, L.I., New York

COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOGY

VOLUME XXIX

Human Genetics

COLD SPRING HARBOR LABORATORY OF QUANTITATIVE BIOLOGY COLD SPRING HARBOR, L.I., NEW YORK

1964

COPYRIGHT ~) 1965 BY

THE COLD SPRING HARBOR

LABORATORY OF QUANTITATIVE BIOLOGY

Library of Congress

Catalog Number: 34-8174

All rights reserved. This book may not be reproduced in whole or in part except by reviewers for the public press without written permission from the publisher.

Printed in ~he U.S.A.

The Symposium Volumes are published by the Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York, and may be purchased directly or through booksellers.

Price of Volume 29-$15.00; (inc. postage). Price subject to change without notice.

FOREWORD

There are many possible ways of organizing a symposium on Human Genetics, and many facets of the subject that could receive greater or less emphasis. I t was felt, in this instance, that comprehensiveness had to be sacrificed in order to keep the meeting to such a size that the participants might discuss their work as much outside the lecture hall as inside; this has been the tradition of the meetings at Cold Spring Harbor, and has contributed greatly to their success and their formative influence on the progress of biology. Therefore, certain aspects of human genetics were deliberately omitted. There was, for example, no discussion devoted strictly to those chromosomal defects recently found associated with certain congenital anomalies, nor was there a section dealing specifically with chromosomal behavior. Instead, the meeting was divided into three sections which dealt with the genetics of human populations, of human cells in culture, and of human proteins. In this way the gamut of disciplines that have contributed to the subject of human genetics as a whole could be represented.

I wish to express our appreciation to Alexander Bearn, Luca Cavalli-Sforza, Harry Eagle, Victor McKusick, Newton Morton, Arno Motulsky, G. Pontecorvo, Arthur Steinberg and Curt Stern, whose generous and thoughtful advice provided the basis for the organization of this program; and also to A. C. Allison, J. Spuhler, W. Szybalski, C. Baglioni, and O. Smithies who served as chairmen of various sessions. We are especially grateful to Drs. Dobzhansky and Glass for their outstanding contributions as Convenor and Summarizer of the meetings. The editor was assisted in the pro- duction of this volume by Harriet D. Hershey.

Some program changes: there was an ad hoc decision that some additional work on human proteins should be presented at this time, and a general discussion section for this was arranged and chaired by Oliver Smithies; although his paper is published in this volume, Dr. Freire Maia was unfortunately unable to attend the meetings.

The meetings this year ran from the 5th to the l l t h of June and were attended by about 150 participants, including 20 from abroad. As in recent years, the program was supported by the National Institutes of Health, U.S. Public Health Service; The National Science Foundation; The U.S. Atomic Energy Commission; and the U.S. Air Force (under grant AF-AFOSR-426-64).

John Cairns, Editor: Leonora Frisch Director

LIST OF PREVIOUS VOLUMES

Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume

Volume

Volume Volume Volume

Volume Volume Volume Volume Volume

I (1933) Surface Phenomena, 239 pp. II (1934) Aspects of Growth, 284 pp. III (1935) Photochemical Reactions, 359 pp. IV (1936) Excitation Phenomena, 376 pp. V (1937) Internal Secretions, 433 pp. VI (1938) Protein Chemistry, 395 pp. VII (1939) Biological Oxidations, 463 pp. VIII (1940) Permeability and the Nature of Cell Membranes, 285 pp. IX (1941) Genes and Chromosomes: Structure and Organization, 315 pp. X (1942) The Relation of Hormones to Development, 167 pp. XI (1946) Heredity and Variation in Microorganisms, 314 pp. XII (1947) Nucleic Acids and Nucleoproteins, 279 pp. XIII (1948) Biological Applications of Tracer Elements, 222 pp. XIV (1949) Amino Acids and Proteins, 217 pp. XV (1950) Origin and Evolution of Man, 425 pp. XVI (1951) Genes and Mutations, 521 pp. XVII (1952) The Neuron, 323 pp. XVIII (1953) Viruses, 301 pp. XIX (1954) The Mammalian Fetus: Physiological Aspects of Develop-

ment, 225 pp. XX (1955) Population Genetics: The Nature and Causes of Genetic Varia-

bility in Populations, 346 pp. XXI (1956) Genetic Mechanisms: Structure and Function, 392 pp. XXII (1957) Population Studies: Animal Ecology and Demography, 437 pp. XXIII (1958) Exchange of Genetic Material: Mechanisms and Conse-

quences, 450 pp. XXIV (1959) Genetics and Twentieth Century Darwinism, 321 pp. XXV (1960) Biological Clocks, 524 pp. XXVI (1961) Cellular Regulatory Mechanisms, 408 pp. XXVII (1962) Basic Mechanisms in Animal Virus Biology, 535 pp. XXVIII (1963) Synthesis and Structure of Macromolecules, 610 pp.

SOME S Y M P O S I U M P A R T I C I P A N T S

T o p row: S. Gart ler , E. Gible t t - R. H. Pos t , V. A. McKusick , J . P . Welch, B. Glass, E. Goldschmidt , J . Su t t e r - B. Glass, T. Dobzhansky .

Second row: S. Tosi, L. DeCarli , R . Tosi - R. D. Koler , L. Herzenberg , D. C. McGuire - H. B. Newcombe , N. E. Morton.

T h i r d row: C. Gajdusek, E. Zuckerkand! - E. Klein , W. Szybalski - L. De Carli, G. Pon tecorvo , B. McClintock. F o u r t h r o w : J . V. 5~eel - H. S. Chandra , Y. Hi ra izumi - H . G. Kunke l , R . E. Rosenberg .

SOME SYMPOSIUM PARTICIPANTS

Top row: K. Wilson, S. Polmar, R. E. Rosenfield, A. G. Steinberg - A. C. Allison, R. S. Krooth - H. Roman, M. Demeree .

S e c o n d r o w : N. H i l s e h m a n , R . Koler , E . R . H u e h n s , D. J . W e a t h e r a l l - A. G. Motu l sky , H . E . K i r k m a n , E . B e u t l e r - J . Cairns, P. Abel , L. Fr i sch , H. D. H e r s h e y .

T h i r d r o w : E. Zucke rkand l , C. Bagl ioni - J . W. Lit t lef ield, S. Champe , H. B. Newcombe , W. Szybalsk i - i . M. Slatis , L. L. Caval l i -Sforza , W. F. B o d m e r , A. G. Motu l sky .

F o u r t h r o w : V. A. McKus ick , I f . W. Lewis - A. G. S te inberg , A. G. B e a m - J . Osmundsen , W. Szybalski , R . Sager .

List of Those Attending the Symposium

ABEL, P., Institut fiir Genetik der Universitat zu Koln, West Germany

ALLISON, A. C., National Institute for Medical Research, London, England

AJMAR, FRANCO, Department of Medicine, Uni- versity of Chicago, Chicago, Illinois

ARIAS C., SERGIO, Div. of Medical Genetics, Moore Clinic, Johns Hopkins Hospital, Baltimore, Maryland

ARONSON, FRANK, C/O Dr. R. P. Cox, Dept. of Medicine, New York University School of Medicine, New York

ARONSON, STANLEY M., Department of Pathology, State University of New York, Downstate Medical Center, Brooklyn, N.Y.

BACH, FRITZ, New York University Medical Center, New York

BAGLIONI, CORRADO, International Laboratory of Genetics and Biophysics, Naples, Italy

BAT-MIRIAM, MARIASSA, Department of Biology, University of Notre Dame, South Bend, Indiana

BAUERLE, RONALD, Cold Spring Harbor Labora- tory of Quantitative Biology, Cold Spring Harbor, New York

BAUMILLER, ROBERT C., Division of Human Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland

BEARN, ALEXANDER G., Department of Human Genetics, Rockefeller Institute, New York

BEETLER, ERNEST, Division of Medicine, City of Hope Medical Center, Duarte, Cali- fornia

BLUME, DORIS, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

BODMER, WALTER F., Department of Genetics, Stanford University Medical School, Stanford, California

BONNE, BATHSHEBA, Department of Biochemistry, Boston University School of Medicine, Boston, Mass.

BOYER, SAMUEL H., Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland

BURGI, ELIZABETH, Genetics Research Unit, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

BURNS, RICHARD, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

CAIRNS, JOHN, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

CALVO, JOSErH, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

CAVALCANTI, A. G. LAGDEN, Universidade do Brasil, Centro de Pesquisas Geneticas, Avenida Antonio Carlos, 40, Rio de Janeiro, Brasil

CAVALLI-SFoRZA, L. L., Istituto di Genetica, Universita di Pavia, Italy

CHAMPE, SEWELL P., Dept. of Biological Sciences, Purdue University, Lafayette, Indiana

CHANDRA, H. SHARAT, Institute for Cancer Re- search, Fox Chase, Philadelphia, Pennsyl- vania

COHEN, MAIMON M., Dept. of Human Genetics, University of Michigan, Ann Arbor, Michigan

CONNEALLY, PATRICK ~IICHAEL, C/O Prof. A. G. Steinberg, Dept. of Biology, Western Reserve University, Cleveland, Ohio

Cox, RODY P., Dept. of Medicine, New York University School of Medicine, New York, N.Y.

DANEK, JOHN J., Nassau County Health Depart- ment, Mineola, N.Y. and Downstate Medical Center, Brooklyn, New York

DAVERN, CEDRIC, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

DAVIDSON, RICHARD, Biology Department, Wes- tern Reserve University, Cleveland, Ohio

DAVIS, JESSICA G., Dept. of Genetics, Albert Einstein College of Medicine, New York, N.Y.

DE CARLI, L., Istituto di Genetica, Universita di Pavia, Italy

DEMEREC, M., Brookhaven National Laboratory, Upton, New York

DOBZHANSKY, TH., The Rockefeller Institute for Medical Research, New York, N.Y.

DRONAMRAJU, K. R., Division of Medical Genetics, Dept. of Medicine, The Johns Hopkins Hos- pital and Medical School, Baltimore, Mary- land.

EAGLE, HARRY, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York

ELDRIDGE, ROSWELL, Johns Hopkins Hospital, Baltimore, Maryland

ERK, FRANK C., Department of Biological Sciences, State University of New York, Stony Brook, New York

FALK, RAPHAEL, Laboratory of Genetics, The Hebrew University, Jerusalem, Israel

FERRARI, IRIS, Dept. of Medical Genetics, Uni- versity of Wisconsin, Madison, Wisconsin

ix

x LIST OF THOSE ATTENDING THE SYMPOSIUI~{

FIELDS, KAY LOUISE, Division of Microbiology, Massachusetts Institute of Technology, Cam- bridge, Mass.

FIRSCHEIN, I. LESTER, New York University Medi- cal Center, New York, N.Y.

FREUNDLICH, MARTIN, Cold Spring Harbor Labora- tory of Quantitative Biology, Cold Spring Harbor, New York

FRISCH, LEONORA, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

FUDENBERG, H. HUGH, University of California, San Francisco Medical Center, San Francisco, California

GAJDUSEK, D. CARLETON, National Institutes of Health, Bethesda, Maryland

GARTLER, STANLEr M., Dept. of Medical Genetics, University of Washington School of Medicine, Seattle, Washington

GIBLETT, ELOISE R., King County Central Blood Bank and Department of Medicine, University of Washington School of Medicine, Seattle, Washington

GLASS, BENTLEY, Department of Biology, Johns Hopkins University, Baltimore, Maryland

GOLDBERG, EDWARD, Genetics Research Unit, Cold Spring Harbor Laboratory of Quantita- tive Biology, Cold Spring Harbor, N.Y.

GOLDSCHMIDT, ELISABETH, Department of Zoology, Laboratory of Genetics, The Hebrew Univer- sity, Jerusalem, Israel

GORDIS, LEON, Sinai Hospital, Baltimore, Maryland GRIFFIN, MARTIN J., 360 W 20 Avenue, New York,

N.Y. GRUNDBACHER, FRED J., Dept. of Human Genetics,

University of Michigan Medical School, Ann Arbor, Michigan

HACKNEY, EDWARD, Cold Spring Harbor Labora- tory of Quantitative Biology, Cold Spring Harbor, New York

HALL, JUDITH GOSLIN, Division of Medical Gene- tics, Department of Medicine, University of Washington, Seattle, Washington

HATHAWAY, PETER, C/O Dr. Samuel H. Boyer, The Johns Hopkins University School of Medicine, Baltimore, Maryland

HECHT, FREDERICK, Division of Medical Genetics, University Hospital, Seattle, Washington

HERSHEY, A. D., Genetics Research Unit, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

HERSHEY, HARRIET, Cold Spring Harbor Labora- tory of Quantitative Biology, Cold Spring Harbor, New York

HERZ, FRITZ, Sinai Hospital, Baltimore, Maryland HERZENBERG, LEONARD A., Stanford University

Medical School, Palo Alto, California

HIRAIZUMI, Y., Dept. of Human Genetics, National Institute of Genetics, Mishima, Sizuoka-Ken, Japan

HUEHNS, E. R., Biochemistry Department, University College London, London, England

HUGHES, ROSCOE D., Medical College of Virginia, Richmond, Virginia

HUNGERFORD, D. A., Institute for Cancer Re- search, Fox Chase, Philadelphia, Pennsylvania

INGRAHAM, LAURA, Genetics Research Unit, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

ITANO, HARVEY A., National Institutes of Health, Bethesda, Maryland

JONES, RICHARD T., Division of Experimental Medicine, University of Oregon Medical School, Portland, Oregon

JOKLIK, W. K., Department of Cell Biology, Albert Einstein College of Medicine, New York, N.Y.

KING, DONALD W., University of Colorado Medical School, Denver, Colorado

KING, JAMES P., Department of Biology, Western Reserve University, c/o Professor Steinberg, Cleveland, Ohio

KIRKMAN, HENRY N., University of Oklahoma Medical Center, Oklahoma City, Oklahoma

KLEIN, EVA, Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden

KNIGHT, DON, c/o Dr. Bearn, Rockefeller In- stitute for Medical Research, New York, N.Y.

KOLER, ROBERT D., Division of Experimental Medicine, University of Oregon Medical School, Portland, Oregon

KOSOWER, N. S., Albert Einstein College of Med- icine, Bronx, N.Y.

KOSSMANN, R. J., National Institutes of Health, Bethesda, Maryland

KRIEGER, HENRIQUE, Department of Genetics, University of Hawaii, Honolulu, Hawaii

KROOTH, ROBERT S., Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan

KUNKEL, HENRY G., The Rockefeller Institute for Medical Research, New York, N.Y.

LEDINKO, NADA, Salk Institute for Biological Research, San Diego, California

LEwis, HERMAN W., Genetic Biology Program, National Science Foundation, Washington, D.C.

LITTLEFIELD, J. W., Massachusetts General Hos- pital, Boston, Mass.

MAcDoWELL, E. CARLETON, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

MACK, CORNELIA, Genetics Department, University of Wisconsin, Madison, Wisconsin

LIST OF THOSE ATTENDING THE SYMPOSIUM xi

MAIO, JOSEPH J., Cell Biology, Albert Einstein Memorial Hospital, New York, N.Y.

MAROOLIN, PAUL, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

MARTIN, GEORGE M., Department of Pathology, University of Washington, Seattle, Washing- ton

MERRITT, A. DONALD, Medical Genetics Program, Indiana University Medical Center, India- napolis, Indiana

MILLER, B., Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

MORTON, NEWTON E., Department of Genetics, University of Hawaii, Honolulu, Hawaii

MOSER, GERTRUDE, Department of Genetics, Albert Einstein Medical College, Bronx, New York

MosIo, GISELA, Genetics Research Unit, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, N.Y.

MOTULSKY, ARNO G., Department of Medical Genetics, University of Washington School of Medicine, Seattle, Washington

MUKAI, FRANK, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

MURPHY, EDMOND A., The Johns Hopkins Hos- pital, Baltimore, Md.

McCLINTOCK, BARBARA, Genetics Research Unit, Cold Spring Harbor Laboratory of Quanti- tative Biology, Cold Spring Harbor, New York

MCCURDY, PAUL R., D.C. General Hospital, Washington, D.C.

McGUIRE, DONALD C., Undergraduate Science Education Program, National Science Foun- dation, Washington, D.C.

McKuslcK, V. A., Department of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland

NANCE, WALTER E., Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

NEEL, J. V., University of Michigan, Ann Arbor, Michigan

NEVO, SARAH, Western Reserve University, Cleve- land, Ohio

NEWCOMBE, H. B., Biology and Health Physics Division, Atomic Energy of Canada, Ltd., Chalk River, Ontario, Canada

NITOWSKY, HAROLD M., Sinai Hospital, Baltimore, Maryland

OVERMIRE, THOMAS G., Undergraduate Science Education Program, National Science Foun- dation, Washington, D.C.

PHILIPS, JOHN, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

POLMAR, STEPHEN, C/O Professor Arthur G. Stein- berg, Department of Biology, Western Re- serve University, Cleveland, Ohio

PONTECORVO, G., Genetics Department, The Uni- versity, Glasgow, Scotland

POST, RICHARD H., University of Michigan, Ann Arbor, Michigan

PUCK, THEODORE T., Department of Biophysics, University of Colorado Medical Center, Den- ver, Colorado

REED, T. EDWARD, Department of Zoology and Paediatrics, University of Toronto, Toronto, Canada

ROMAN, HERSCHEL L., Department of Genetics, University of Washington, Seattle, Washing- ton

ROSENEERG, MARVIN, Cold Spring Harbor Labora- tory of Quantitative Biology, Cold Spring Harbor, New York, and State University, Stony Brook, New York and Columbia University, New York

ROSENFIELD, RICHARD E., Department of Hema- tology, The Mount Sinai Hospital, New York, N.Y.

SEEGERS, WINIFRED, New York University Med- ical Center, New York

SHAW, MARGERY W., Dept. of Human Gene- tics, University of Michigan, Ann Arbor, Michigan

SILAGI, SELMA, The Rockefeller Institute for Medical Research, New York, N.Y.

SILVERSTEIN, EMANUEL, State University of New York, Downstate Medical Center, Brooklyn, New York

SIu, PATRICK, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York

SLATIS, HERMAN M., Department of Zoology, Michigan State University, East Lansing, Michigan

SMITHIES, OLIVER, Department of Medical Genet- ics, University of Wisconsin Medical School, Madison, Wisconsin

SPUHLER, J. N., Department of Anthropology and Human Genetics, University of Michigan, Ann Arbor, Michigan

SPUHLER, HELEN, Department of Anthropology and Human Genetics, University of Michigan, Ann Arbor, Michigan

STEINBERG, ARTHUR G., Department of Biology, Western Reserve University, Cleveland, Ohio

SUTTER, JEAN, Institut National d'Etudes Demo- graphique, Paris, France

xii LIST OF THOSE ATTENDING THE SYMPOSIUM

SUTTON, H. ELDON, Department of Zoology, University of Texas, Austin, Texas

SZYBALSKI, WACLAW, McArdle Memorial Labora- tory, University of Wisconsin Medical School, Madison, Wisconsin

TAKANAMI, M.ITURU, Brookhaven National Labora- tory, Upton, New York

TosI, ROBERTO, Department of Bacteriology and Immunology, Harvard Medical School, Boston, Mass.

TosI, SIMONETTA, Children's Hospital Medical Center, Boston, Mass.

WAELSCH, SALOME G., Albert Einstein College of Medicine, Dept. of Genetics, New York, N.Y.

WARBURTO~, F. E., Department of Zoology, Columbia University (Barnard College), New York, N.Y.

WEATHERALL, DAVID J., Johns Hopkins Hospital, Baltimore, Md.

WELCH, J. PHILIP, The Moore Clinic, Johns Hop- kins Hospital, Baltimore, Maryland

WILSON, JANET, C/O Professor Arthur G. Steinberg, Department of Biology, Western Reserve University, Cleveland, Ohio

WILSO.~, KATHERISE S., Division of Research Grants, National Institutes of Health, Beth- esda, Maryland

YuNIs, JORGE J., Department of Laboratory Medicine, University of Minnesota Hospitals, Minneapolis, Minnesota

ZUBOr, GEOFFREr, Biology Department, Brook- haven National Laboratory, Upton, New York

ZUCKERKANDL, EMILE, Laboratoire de Physico- Chimie, Colloidalc du CNRS, Montpelier, France

ZUCKERKANDL, MRS. EMILE, Laboratoire de Physi- co-Chimie, Colloidale du CNRS, Montpelier, France

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v List of Previous Volumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi Photographs of Some Symposium Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . vii List of Those Attending the Symposium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

TH. DOBZHANSKY. Opening Address: Human Genetics--An Outsider's View 1

POPULATION STUDIES

CAVXLLI-SFoRZA, L. L., I. BARRAI and A. W. F. EDWARDS. Analysis of Human Evolution under Random Genetic Drift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

NEWCOMBE, H. B. Pedigrees for Population Studies--A Progress Report . . . . 21 FREIRE-MAIA, N. On the Methods Available for Estimating the Load of Muta-

tions Disclosed by Inbreeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 SUTTER, J. and J. M. Goux. Lethal Equivalents and Demographic Measures of

Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 HIRAIZUMI, Y. Prezygotic Selection as a Factor in the Maintenance of Varia-

bility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 SLATIS, H. The Study of Normal Variation in Man. I I . Polymorphism and Plei-

otropy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 MORTON, N. E. Genetic Studies of Northeastern Brazil . . . . . . . . . . . . . . . . . . . 69 DRONAMRAJU, K. R. Mating Systems of the Andhra Pradesh People . . . . . . . . 81 NEEL, t]'. and F. SALZANO. A Prospectus for Genetic Studies of the American

Indian . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 McKusIcK, V. A., J. A. HOSTETLER, J. A. EGELAND, and R. ELDRIDGE. The

Distribution of Certain Genes in the Old Order Amish . . . . . . . . . . . . . . . . 99 GOLDSCHMIDT, E. and T. COHEN. Inter-ethnic Mixture among the Communities

of Israel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 GAJDUSEK, D. C. Factors Governing the Genetics of Primitive Human Pop-

ulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 ALLISON, A. C. Polymorphism and Natural Selection in Human Populations .. 137

GENETICS OF SOMATIC CELLS AND CELLS IN CULTURE

SZYBALSKI, W. Chemical Reactivity of Chromosomal DNA as Related to Muta- genicity: Studies with Human Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

LITTLEFIELD, J. W. The Selection of Hybrid Mouse Fibroblasts . . . . . . . . . . . 161 PUCK, T. T. Studies of the Life Cycle of Mammalian Cells . . . . . . . . . . . . . . . . . 167 GLASS, B. The Study of Gene and Chromosome Mutations in Human and Other

Mammalian Cell Cultures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 ABEL, P. Evidence for the Universality of the Genetic Code . . . . . . . . . . . . . . . . . 185 KROOTH, R. S. Properties of Diploid Cell Strains Developed from Patients with

an Inherited Abnormality of Uridine Biosynthesis . . . . . . . . . . . . . . . . . . . . 189 KOLER, R., R. BIGLEY, R. T. JONES, D. A. RIGAS, P. VANBELLINGHEN, and P.

THOMPSON. Pyruvate Kinase: Molecular Differences between Human Red Cell and Leukocyte Enzyme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

DE C~mLI, L., J. J. MAIo, F. Nuzzo, and A. S. BENERECETTI. Cytogenetic Studies with Alkaline Phosphatase in Human Heteroploid Cells . . . . . . . . . . . . . . . 223

Cox, R. P., and C. M. MACLEOD. Regulation of Alkaline Phosphatase in Human Cell Cultures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233

GARTLER, S. M. and D. LINDER. Selection in Mammalian Mosaic Cell Popu- lations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

BEUTLER, E. Gene Inactivation: The Distribution of Gene Products among Populations of Cells in Heterozygous Humans . . . . . . . . . . . . . . . . . . . . . . . . 261

xiii

xiv CONTENTS

KLEIN, E. Transplantation Antigens as Markers in Somatic Cell Genetics . . 273 PAYNE, R., M. TRIPP, J. WEIGLE, W. BODMER, and J. BODMER. A New Leuko-

cyte Isoantigen System in Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

HUMAN P R O T E I N S

JONES, R. T. Structural Studies of Aminoethylated Hemoglobins by Automatic Peptide Chromatography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

SMITHIES, O. Chromosomal Rearrangements and Protein Structure . . . . . . . . . 309 GIBLETT, E. Variant Haptoglobin Phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 HUEHNS, E. R., N. DANCE, G. H. BEAVEN, F. HECHT, and A. G. MOTULSKY.

Human Embryonic Hemoglobins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 BOYER, S. H., P. HATHAWAY, and M. D. GARRICK. Modulation of Protein Syn-

thesis in Man: An in vitro Study of Hemoglobin Synthesis by Heterozy- gotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333

BAGLIONI, C. and B. COLOMBO. Control of Hemoglobin Synthesis . . . . . . . . . . . . 347 ZUCKERKANDL, E. Compensatory Effects in the Synthesis of Hemoglobin Poly-

peptide Chains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357 KOSSMANN, R. J. , D. C. FAINER, and S. H. BOYER. A Study of Myoglobin in

Disease with Comments Concerning the Myoglobin Minor Components . . . 375 HUEHNS, E. R., D. J . WEATHERALL, R. H. DE BELLIS, L. LUZZATTO. General

Discussion: Human Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 KIRKMAN, H. N., P. R. MCCURDY, and J. L. NAIMXN. Functionally Abnormal

Glucose-6-Phosphate Dehydrogenases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 MOTULSKY, A. G. Current Concepts of the Genetics of the Thalassemias . . . . . . . 399 NANCE, W. E. Genetic Tests with a Sex-linked Marker: Glucose-6-Phosphate

Dehydrogenase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415 ROSENFIELD, R. E., I. O. SZYMANSKI, and S. KOCHWA. Immunochemical Studies

of the Rh System. I I I . Quantitative Hemagglutination that is Relatively Independent of Source of Rh Antigens and Antibodies . . . . . . . . . . . . . . . . 427

BEARN, A. G., B. H. BOWMAN, and F. D. KITC~IN. Genetic and Biochemical Considerations of the Serum Group-Specific Component . . . . . . . . . . . . . . . 435

KUNKEL, H. G., J. C. ALLEN, and H. M. GREY. Genetic Characters and the Polypeptide Chains of Various Types of Gamma Globulin . . . . . . . . . . . . . 443

STEINBERG, A. G. Population, Immunogenetic, and Biochemical Studies on the Gin(b) Factors of Human Gamma Globulin . . . . . . . . . . . . . . . . . . . . . . . . . . 449

HERZENBERG, L. A. A Chromosome Region for Gamma 2a and Beta 2A Globulin H Chain Isoantigens in the Mouse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455

FUDENBERG, H. H., E. R. STIEHM, E. C. FRANKLIN, M. MELTZER, and B. FRAN- GIONE. Antigenicity of Hereditary Human y-Globulin (Gm) Factors--Bio- logical and Biochemical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463

GLASS, B. Summary and Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . 473