The Charles B' Huggins Lectures, 2006

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• The Charles B. Huggins Lectures, 2006
• Breast Cancer
• the Genetics of a Disease
• James D. Fackenthal, Ph.D.
• University of Chicago

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The Charles B. Huggins Lectures, 2006 Saturdays
from 1100 AM 1200 PM
Jan 14. Overview and introduction to
cancer Jan 21. Early experiments in genetics
the science of heredity Jan 28. Later
experiments in genetics the science of
molecular biology Feb 4. The DNA double
helix structural basis of heredity and
molecular biology
Feb 11. Gene mutations and cancer, part 1
oncogenes and tumor suppressor genes regulate
tumor development Feb 18. Gene mutations and
cancer, part 2 hormone action in normal
cells and breast tumors Feb 25. Genetic
studies point the way to better
treatments March 4. From Genetics to
Genomics.
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Breast Cancer Staging
The overall stage of the tumor is described by a
Roman numeral (I-IV).

T1, N0, M0 Stage IT4, N3, M1 Stage IV
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Gregor Mendel (1822-1884)
Versuche über Pflanzen-Hybriden (1866)
Proceedings of the Society of the Natural
Sciences
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Flower parts
Prunus sp.
Starr, C. and Taggart, R (1984) Biology The
Unity and Diversity of Life. Wadsworth, Inc.
Belmont, CA
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Flower manipulation
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Flower traits phenotypes
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Mendels results
What does it mean?
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Mendels interpretations
1) Traits (phenotypes) are determined by two
factors, one from the father, and one from the
mother. 2) The maternally and paternally
inherited factors may be variants of the same
factor (alleles). 3) One allele may mask the
phenotype associated with the other allele
(dominant vs. recessive alleles).
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How does this work? Genotypes.
Cross parental strains (P) to produce the first
filial generation (F1).
Round seeds (R/R)
R R
Wrinkly seeds (r/r)
r r
R/r R/r R/r R/r
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How does this work? Genotypes.
Cross first filial generation (F1) plants to
produce the second filial generation (F2).
Round seeds (R/r)
R r
Round seeds (R/r)
R r
R/R R/r R/r r/r
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Mendels first law Segregation
Two members of a gene pair segregate from each
other into the gametes, so that one-half of the
gametes carry one member of the pair and the
other one-half of the gametes carry the other
half of the pair.
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Two phenotypes considered together
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Two phenotypes considered together
Male F1 (R/r Y/y)
Female F1 (R/r Y/y)
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Mendels second law Independent assortment
During gamete formation the segregation of
alleles of one gene is independent of the
segregation of the alleles of another gene.
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Chromosomal theory of inheritance
Starr, C. and Taggart, R (1984) Biology The
Unity and Diversity of Life. Wadsworth, Inc.
Belmont, CA
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Cell Division
Nucleus
From Molecular Biology of the Cell by Alberts et
al. (4th ed) Garland Science Textbooks, New York,
NY c2002
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Chromosomes and cell division Mitosis and meiosis
Watson et al. (1983) Recombinant DNA A Short
Course Scientific American Books, New York, NY
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Landmarks in the chromosomal theory of inheritance
1905 Edmond Wilson and Nettie Stevens (working
in Hemiptera) described the X-chromosome in males
and noted that the segregation of chromosomes in
meiosis paralleled the conceptual idea of genes
segregating during gamete formation. 1910
Thomas Hunt Morgan demonstrated directly that X
and Y chromosomes determine sex and showed that
genes on the X chromosome could be mutated.
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Landmarks in the chromosomal theory of inheritance
1911 Alfred Sturtevant devised recombination
maps that defined the physical relationship
between genes (linkage).
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Sturtevants linkage analysis
Purple eyes pr/pr Normal (wild type)
eyes pr/pr or pr/pr Vestigial
wings vg/vg Normal (wild type)
wings vg/vg or vg/vg
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Sturtevants linkage analysis
wild type eyes, wild type wings
purple eyes, vestigial wings
X
purple eyes, vestigial wings
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wild type eyes, wild type wings
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purple eyes, wild type wings
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5
wild type eyes, vestigial wings
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Sturtevants linkage analysis
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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Pedigree analysis
Griffiths et al. (1993) An Introduction to
Genetic Analysis (5th ed. ). WH Freeman and Co.
New York, NY
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BRCA1 and BRCA2 were identified by pedigree and
linkage analysis
Couch and Weber Breast Cancer in The Genetic
Basis of Human Cancer, Vogelstein and Kinzler,
eds. McGraw-Hill, New York, 1998
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Major Points
Genes come in pairs that separate from each
other (segregate) when gametes are formed.
Genes can become mutated to produce different
phenotypes.
Different versions of genes (alleles) can
behave in a dominant or recessive manner in the
presence of other alleles.
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Major Points
Genes reside within chromosomes like beads on
a string.
Genes on the same chromosome are linked, but
genes on different chromosomes assort
independently.
New genes can be identified using linkage
analysis based on recombination frequencies
between known genes.