Wilhelm Weinberg
Encyclopedia
Dr Wilhelm Weinberg was a German half-Jewish physician and obstetrician-gynecologist, practicing in Stuttgart
, who in a 1908 paper (Jahresheft des Vereins für vaterländische Naturkunde in Württemberg (Annals of the Society of the National Natural History in Württemberg) published in German, expressed the concept that would later come to be known as the Hardy-Weinberg principle
.
Weinberg is also credited as the first to explain the effect of ascertainment bias on observations in genetics.
independently of British mathematician G.H. Hardy. He delivered an exposition of his ideas in a lecture on January 13, 1908, before the Verein für vaterländische Naturkunde in Württemberg (Society for the Natural History of the Fatherland in Württemberg), about six months before Hardy's paper was published in English. His lecture was printed later that year in the society's yearbook.
Weinberg's contributions were unrecognized in the English speaking world
for more than 35 years. Curt Stern, a German scientist who immigrated to the United States before World War II
, pointed out in a brief paper in Science that Weinberg's exposition was both earlier and more comprehensive than Hardy's. Before 1943, the concepts in genetic equilibrium
that are known today as the Hardy-Weinberg principle
had been known as "Hardy's law" or "Hardy's formula" in English language texts.
James F. Crow
writes: “Why was Weinberg’s paper, published the same year as Hardy’s, neglected for 35 years? The reason, I am sure, is that he wrote in German. At the time, genetics was largely dominated by English speakers and, sadly, work in other languages was often ignored.”
variation that partitioned this variance into genetic and environmental components. In the process, he recognized that ascertainment bias was affecting many of his calculations, and he produced methods to correct for it.
Weinberg observed that proportions of homozygotes in familial studies of classic autosomal recessive genetic diseases generally exceed the expected Mendelian ratio of 1:4, and he explained how this is the result of ascertainment bias. In his work with albino children, he recognized that in some families where both parents carry a recessive mutation, no disease occurs by chance. He reasoned that many carrier couples were not being counted, and he demonstrated methods for correcting results to produce the expected Mendelian ratios.
He discovered the answer to several seeming paradoxes caused by ascertainment bias. For example, he explained that the reason that parents as a whole are more fertile than their children is because children must necessarily come from fertile parents.
By the same token, he recognized that ascertainment was responsible for a phenomenon known as anticipation
, the tendency for a genetic disease to manifest earlier in life and with increased severity in later generations. Weinberg recognized that this was because those later generations were the offspring of that selected group of earlier carriers that had successfully reproduced. Subsequent researchers have reasoned that such carriers who reproduce might be expected to carry favorable genetic modifiers that allowed them to reproduce successfully in spite of their disease. In a class of autosomal and X-linked dominant
diseases known as trinucleotide repeat disorders
(for example, Huntington’s disease), a molecular mechanism for anticipation has also been demonstrated. It is caused by the instability of repeating nucleotide
sequences that tend to undergo expansion, causing disease at an earlier and earlier age as trinucleotide repeats accumulate.
and studied medicine
at Tübingen
, Berlin
and Munich
, receiving an M.D. in 1886. He returned to Stuttgart
in 1889, where he remained running a large practice as a gynecologist and obstetrician until he retired to Tübingen
a few years before his death in 1937. Much of his academic life he spent studying genetics
especially focusing on applying the laws of inheritance to populations.
Additional contributions by Weinberg to statistical genetics included the first estimate of the rate of twinning – Realizing that identical twins would have to be same-sex, while dizygotic twins could be either same or opposite sex, Weinberg derived the formula for estimating the frequency of monozygotic and dizygotic twins from the ratio of same sex and opposite twins to the total of maternities. Weinberg also estimated that the heritability of twinning itself was close to zero.
Stuttgart
Stuttgart is the capital of the state of Baden-Württemberg in southern Germany. The sixth-largest city in Germany, Stuttgart has a population of 600,038 while the metropolitan area has a population of 5.3 million ....
, who in a 1908 paper (Jahresheft des Vereins für vaterländische Naturkunde in Württemberg (Annals of the Society of the National Natural History in Württemberg) published in German, expressed the concept that would later come to be known as the Hardy-Weinberg principle
Hardy-Weinberg principle
The Hardy–Weinberg principle states that both allele and genotype frequencies in a population remain constant—that is, they are in equilibrium—from generation to generation unless specific disturbing influences are introduced...
.
Weinberg is also credited as the first to explain the effect of ascertainment bias on observations in genetics.
Hardy-Weinberg principle
Weinberg developed the principle of genetic equilibriumGenetic equilibrium
A genetic equilibrium is at hand for an allele in a gene pool when the frequency of that allele is not changing . For this to be the case, evolutionary forces acting upon the allele must be equal and opposite. The only basic requirement is that the population be large enough that the effects of...
independently of British mathematician G.H. Hardy. He delivered an exposition of his ideas in a lecture on January 13, 1908, before the Verein für vaterländische Naturkunde in Württemberg (Society for the Natural History of the Fatherland in Württemberg), about six months before Hardy's paper was published in English. His lecture was printed later that year in the society's yearbook.
Weinberg's contributions were unrecognized in the English speaking world
Anglosphere
Anglosphere is a neologism which refers to those nations with English as the most common language. The term can be used more specifically to refer to those nations which share certain characteristics within their cultures based on a linguistic heritage, through being former British colonies...
for more than 35 years. Curt Stern, a German scientist who immigrated to the United States before World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, pointed out in a brief paper in Science that Weinberg's exposition was both earlier and more comprehensive than Hardy's. Before 1943, the concepts in genetic equilibrium
Genetic equilibrium
A genetic equilibrium is at hand for an allele in a gene pool when the frequency of that allele is not changing . For this to be the case, evolutionary forces acting upon the allele must be equal and opposite. The only basic requirement is that the population be large enough that the effects of...
that are known today as the Hardy-Weinberg principle
Hardy-Weinberg principle
The Hardy–Weinberg principle states that both allele and genotype frequencies in a population remain constant—that is, they are in equilibrium—from generation to generation unless specific disturbing influences are introduced...
had been known as "Hardy's law" or "Hardy's formula" in English language texts.
James F. Crow
James F. Crow
James F. Crow is Professor Emeritus of Genetics at the University of Wisconsin–Madison.Some of his most significant peer-reviewed contributions were coauthored with Motoo Kimura. His major contribution to the field, however, is arguably his teaching...
writes: “Why was Weinberg’s paper, published the same year as Hardy’s, neglected for 35 years? The reason, I am sure, is that he wrote in German. At the time, genetics was largely dominated by English speakers and, sadly, work in other languages was often ignored.”
Ascertainment bias and analysis of phenotypic variance
Weinberg pioneered in studies of twins, developing techniques for analysis of phenotypicPhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
variation that partitioned this variance into genetic and environmental components. In the process, he recognized that ascertainment bias was affecting many of his calculations, and he produced methods to correct for it.
Weinberg observed that proportions of homozygotes in familial studies of classic autosomal recessive genetic diseases generally exceed the expected Mendelian ratio of 1:4, and he explained how this is the result of ascertainment bias. In his work with albino children, he recognized that in some families where both parents carry a recessive mutation, no disease occurs by chance. He reasoned that many carrier couples were not being counted, and he demonstrated methods for correcting results to produce the expected Mendelian ratios.
He discovered the answer to several seeming paradoxes caused by ascertainment bias. For example, he explained that the reason that parents as a whole are more fertile than their children is because children must necessarily come from fertile parents.
By the same token, he recognized that ascertainment was responsible for a phenomenon known as anticipation
Anticipation (genetics)
In genetics, anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation. In most cases, an increase of severity of symptoms is also noted. Anticipation is common in trinucleotide repeat disorders such as...
, the tendency for a genetic disease to manifest earlier in life and with increased severity in later generations. Weinberg recognized that this was because those later generations were the offspring of that selected group of earlier carriers that had successfully reproduced. Subsequent researchers have reasoned that such carriers who reproduce might be expected to carry favorable genetic modifiers that allowed them to reproduce successfully in spite of their disease. In a class of autosomal and X-linked dominant
X-linked dominant
X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type...
diseases known as trinucleotide repeat disorders
Trinucleotide repeat disorders
Trinucleotide repeat disorders are a set of genetic disorders caused by trinucleotide repeat expansion, a kind of mutation where trinucleotide repeats in certain genes exceeding the normal, stable, threshold, which differs per gene...
(for example, Huntington’s disease), a molecular mechanism for anticipation has also been demonstrated. It is caused by the instability of repeating nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequences that tend to undergo expansion, causing disease at an earlier and earlier age as trinucleotide repeats accumulate.
Biography
Weinberg was born in StuttgartStuttgart
Stuttgart is the capital of the state of Baden-Württemberg in southern Germany. The sixth-largest city in Germany, Stuttgart has a population of 600,038 while the metropolitan area has a population of 5.3 million ....
and studied medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
at Tübingen
Tübingen
Tübingen is a traditional university town in central Baden-Württemberg, Germany. It is situated south of the state capital, Stuttgart, on a ridge between the Neckar and Ammer rivers.-Geography:...
, Berlin
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...
and Munich
Munich
Munich The city's motto is "" . Before 2006, it was "Weltstadt mit Herz" . Its native name, , is derived from the Old High German Munichen, meaning "by the monks' place". The city's name derives from the monks of the Benedictine order who founded the city; hence the monk depicted on the city's coat...
, receiving an M.D. in 1886. He returned to Stuttgart
Stuttgart
Stuttgart is the capital of the state of Baden-Württemberg in southern Germany. The sixth-largest city in Germany, Stuttgart has a population of 600,038 while the metropolitan area has a population of 5.3 million ....
in 1889, where he remained running a large practice as a gynecologist and obstetrician until he retired to Tübingen
Tübingen
Tübingen is a traditional university town in central Baden-Württemberg, Germany. It is situated south of the state capital, Stuttgart, on a ridge between the Neckar and Ammer rivers.-Geography:...
a few years before his death in 1937. Much of his academic life he spent studying genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
especially focusing on applying the laws of inheritance to populations.
Additional contributions by Weinberg to statistical genetics included the first estimate of the rate of twinning – Realizing that identical twins would have to be same-sex, while dizygotic twins could be either same or opposite sex, Weinberg derived the formula for estimating the frequency of monozygotic and dizygotic twins from the ratio of same sex and opposite twins to the total of maternities. Weinberg also estimated that the heritability of twinning itself was close to zero.