P1247176260aQjZO

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Lecture 10 Genetics Patterns of Inheritance in
Humans
Readings Ch. 14, 14.4 to end
You need to be able to explain the following to
yourself and to me (on exams)
Pedigree analysis for determining patterns of
inheritance in humans. reasons, symbols  Five
categories of genetic diseases observed in
humans. single gene (Mendelian) disorders
multifactorial (polygenic) traits chromosomal
abnormalities mitochondrial inheritance
diseases of unknown etiology Examples of
single-gne recessive traits be able to identify
the pattern of inheritance. cystic fibrosis
Tay-Sachs sickle cell disease Examples of
single-gene dominant traits be able to identify
the pattern of inheritance. Huntington Disease
Examples of multifactorial traits be able to
identify the pattern of inheritance. blood
pressure Examples of mitochondrial traits be
able to identify the pattern of inheritance.
Lebers hereditary optic neuropathy Forensic DNA
analysis microsatellite locus
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Pedigree analysis reasons symbols
Single gene traits studied using a pedigree
Why do we need to study pedigrees to understand
Mendelian inheritance in humans?
Because The human generation time is about 20
years. Humans produce relatively few offspring
compared to most other species. Well-planned
breeding experiments are impossible.
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Pedigree analysis reasons symbols
Conventional Symbols for Human Pedigrees
Mating
Normal male
Normal female
Normal, sex irrelevant or unknown
Between relatives
Affected male
Affected female
I
Affected, sex irrelevant or unknown
II
Last born
Sibling birth order from left to right
siblings
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Figure 14.14 Pedigree analysis
Pedigree analysis reasons symbols
We will return to this figure for details
Widows peak
Attached ear lobe
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Five categories of diseases single gene
disorders multifactorial traits mitochondrial
inheritance
Five general categories of genetic disorders exist

• Single gene (Mendelian) disorders
• Polygenic (multifactorial) traits
• Mitochondrial diseases
• Chromosomal abnormalities (Lectures 10, 12)
• Diseases of unknown etiology (causes) that run
  in families

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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Recessive pedigree patterns
Many people in these pedigrees were probably
carriers - heterozygotes
Strictly speaking, these are autosomal recessive
patterns - autosomal means not on sex chromosomes
- we will cover this in detail soon.
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Figure 14.14 Pedigree analysis
Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Widows peak
Attached ear lobe recessive
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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Genetic diseases to know for IB150(in Chapter
14)

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Achondroplasia autosomal dominant form of
  dwarfism
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Autosomal dominant pedigree example
No carriers
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Figure 14.14 Pedigree analysis
Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Widows peak dominant
Attached ear lobe recessive
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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Achondroplasia autosomal dominant form of
  dwarfism
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Examples of multifactorial ( polygenic
inheritance) diseases
Heart disease, hypertension, diabetes,
obesity, many cancers, cleft palate (and many
more)
On a pedigree, polygenic diseases do tend to run
in families, but the inheritance does not fit
simple patterns as with Mendelian diseases. But
this does not mean that the genes cannot
eventually be located and studied. There is also
a strong environmental component to many of them
(e.g., blood pressure).
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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Achondroplasia autosomal dominant form of
  dwarfism
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Mitochondrial DNA
Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance

• Extranuclear DNA
• Humans 16,000 bases
• Not a linear chromosome
• Similar to bacterial DNA
• 37 genes

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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Mitochondrial inheritance
Maternal inheritance
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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Mitochondrial Patterns of Inheritance
Most mitochondrial genes are associated
with metabolism - energy production - so
mitochondrial disorders often involve metabolism
(Lebers hereditary optic neuropathy - causes
loss of central vision - not enough cellular
energy provided to the cells in the retina)
In this case pedigree analysis is simple
All children of affected males WILL NOT inherit
the disease.  All children of affected females
WILL inherit it. There are NO carriers.
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Five categories of diseases single gene
disorders rrecessive
dominant multifactorial traits mitochondrial
inheritance
Genetic diseases to know for IB150

• Tay-Sachs disease single gene, autosomal
  recessive, early lethal, no homozygotes
  reproduce, carriers have normal phenotype
• Sickle cell anemia single gene, autosomal
  recessive, condition can be treated, carriers may
  have symptoms (sickle cell trait)
• Cystic fibrosis single gene, autosomal
  recessive, life can be prolonged, carriers have
  normal phenotype
• Phenylketonuria (PKU) single gene, autosomal
  recessive, can be diagnosed at birth, diet can
  treat, carriers have normal phenotype
• Huntingtons disease single gene, autosomal
  dominant, onset late in life (so patients likely
  to reproduce prior to diagnosis), no carriers
• Achondroplasia autosomal dominant form of
  dwarfism
• Heart disease, high blood pressure multiple
  genes, no simple pattern of inheritance, genes
  increase susceptibility
• Lebers hereditary neuropathy mitochondrial,
  relatively late onset, inherited from mother only

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Forensic DNA analysis microsatellite locus
A recent development in human genetics is the
area of forensic DNA analysis, which is devoted
to identifying humans using hypervariable regions
of DNA. These are typically outside of the genes
themselves. Remember my analogy about genome size
- junk DNA Large genome XRHJCUNYHTRPKLSJTHISIS
GENEAUIXXVXVXVXVHYTINHBTMHBYMTIDIDJMNTHISISGENEBMM
MMZNMENENGUHTTTMNTHEISMMMMETUTHISISGENECNBUUNYBLIH
IUBWERJBOUWEJBRPJBEUBNEM
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Forensic DNA analysis microsatellite locus
Many mutations accumulate in the non-coding DNA.
One type is called a microsatellite locus
(position on a chromosome). The replication
enzymes stutter on repeats and insert
more TIME 1XRHJCUNYHTRPKLSJTHISISGENEAUIXXRTMA
1 repeat TIME 2XRHJCUCUNYHTRPKLSJTHISISGENEA
UIXXRTMA 2 repeats TIME 3XRHJCUCUCUNYHTRPKLSJT
HISISGENEAUIXXRTMA 3 repeats Mutations
constantly occur, and cause different
microsatellite alleles to accumulate in
populations.
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Forensic DNA analysis microsatellite locus
Pedigree for human family K21 variable for a CA
repeat.
The sAVA3 region of 100 bp has been amplified,
and the DNA fragments separated on a
electrophoretic gel (smaller runs faster).
Run direction
size markers
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Forensic DNA analysis microsatellite locus
Pedigree for human family K21 variable for a CA
repeat.
Three alleles were found allele 100 has 21 CA
repeats allele 102 has 22 CA repeats allele 104
has 23 CA repeats allele 110 has 26 CA repeats
ALLELE 1
TAGGTCGAGTCAGGCCCCTACACACACACACACACACACACACACACAC
ACACACACACACATGBAGARAGGGTABGTA
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Forensic DNA analysis microsatellite locus
Pedigree for human family K21 variable for a CA
repeat.
NOTE THE MENDELIAN SEGREGATION OF THE ALLELES!
ALLELE 1
TAGGTCGAGTCAGGCCCCTACACACACACACACACACACACACACACAC
ACACACACACACATGBAGARAGGGTABGTA
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Forensic DNA analysis microsatellite locus
Pedigree for human family K21 variable for a CA
repeat.
MANY MICROSATELLITE LOCI (PLURAL OF LOCUS) HAVE
AS AS MANY AS 50 ALLELES (!), SO THAT AN
EXTREMELY LARGE NUMBER OF GENOTYPES ARE POSSIBLE
(AND DO OCCUR). THUS WE ARE ALL UNIQUE!
ALLELE 1
TAGGTCGAGTCAGGCCCCTACACACACACACACACACACACACACACAC
ACACACACACACATGBAGARAGGGTABGTA
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Reference Vocero-Akbani A., C. Helms, J.-C.
Wang, F.J. Sanjurjo, J. Korte-Sarfaty, R.A.
Veile, L. Liu, A. Jauch, A.K. Burgess, A.V. Hing,
M.S. Holt, S Ramachandra, A.J. Whelan, R. Anker,
L. Ahrent, M. Chen, M.R. Gavin, K. Iannantuoni,
S.M. Morton, S.D. Pandit, C.M. Read, T.
Steinbrueck, C. Warlick, D.A. Smoller, and H.
Donis-Keller. Mapping human telomere regions with
YAC and P1 clones Chromosome specific markers
for 27 telomeres including 149 STSs and 24
polymorphisms for 14 proterminal regions.
Genomics 36492-506 (1996).
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Lecture 10 Genetics Patterns of Inheritance in
Humans
Readings Ch. 14, 14.4 to end
You need to be able to explain the following to
yourself and to me (on exams)
Pedigree analysis for determining patterns of
inheritance in humans. reasons, symbols  Five
categories of genetic diseases observed in
humans. single gene (Mendelian) disorders
multifactorial (polygenic) traits chromosomal
abnormalities mitochondrial inheritance
diseases of unknown etiology Examples of
single-gne recessive traits be able to identify
the pattern of inheritance. cystic fibrosis
Tay-Sachs sickle cell disease Examples of
single-gene dominant traits be able to identify
the pattern of inheritance. Huntington Disease
Examples of multifactorial traits be able to
identify the pattern of inheritance. blood
pressure Examples of mitochondrial traits be
able to identify the pattern of inheritance.
Lebers hereditary optic neuropathy Forensic DNA
analysis microsatellite locus