Patterns of Inheritance

Gregor Mendel’s monastery

General Categories of Inheritance Patterns
• Autosomal inheritance
• Based on variation of single genes on regular chromosomes (autosomes)
• Sex-linked inheritance
• Based on variation of single genes on the sex-determining chromosomes
• Cytoplasmic inheritance
• Based on variation of single genes on organelle chromosomes
Autosomal Inheritance
• Discovered by Gregor Mendel, the Father of Genetics
• Pattern of inheritance observed for genes located on the autosomal
chromosomes, which are all the chromosomes in the cell nucleus except the
sex chromosomes.
The seven character differences studied by Mendel
Mendel’s cross of female white-flowered x male Mendel’s cross of female purple-flowered x male
purple-flowered showed that all progeny of a white-flowered yielded all purple-flowered
reciprocal cross were also purple-flowered. progeny
Results of All Mendel’s Crosses in Which Parents Differed in One Character
Mendel’s explanation of the 1 :2: 1 ratio
 Mendelian 1st law: Law of Segregation
Gamete formation
• Each individual has a pair of factors
(alleles) for each trait
A a
• Alleles segregate (separate) during
gamete (sperm & egg) formation A a

• One gamete = one allele

A a

A A a a
Mendel’s Laws of Genetics
• Law of segregation
• The two members of a gene pair segregate
from each other into the gametes
• Half the gametes carry one member of the
pair and the other half of the gametes
carry the other member of the pair.

The cross of a presumed heterozygote Yy

to a presumed homozygous recessive yy
produces progeny in the ratio 1 : 1.
 Mendelian 1st law: Law of Segregation
• Dominant allele (capital letter) masks the
expression of the recessive allele (lower-case)
Genotype
AA Aa aa
Homozygous Heterozygous Recessive
Dominant Dominant

Purple Purple White

Phenotype
Homozygous = identical alleles / Heterozygous = different alleles
 Mendelian 1st law: Law of Segregation
• One gamete from each parent combines after fertilization

Aa Male Aa Female

A a A a

AA Aa Aa 1
aa
1 2
3:1 ratio
 Mendelian 2nd law: Law of Independent Assortment

• The pair of alleles for one trait

segregate independently of
alleles for other traits
Mendelian 2nd law: Law of Independent Assortment

Allele 1: Color Allele 2: Shape

Cc Male Cc Female Ss Male Ss Female

C c C c S s S s

CC Cc Cc cc SS Ss Ss ss
1 2 1 1 2 1

Treat separately
Mendel’s Laws of Genetics
• Law of independent assortment
• Different gene pairs assort
independently in gamete formation.

A Punnett shows the predicted

genotypic and phenotypic constitution
of the F2 generation from a dihybrid
cross.
 Exercise
Gene A is dominant for colored/ gene a is recessive for albino
Gene D is dominant for hearing/ gene d is recessive for deafness

Albino with Albino and deaf

normal hearing
aaDD Father Mother aadd
aaDd Will all children be albino or deaf or both?

aaDD X aadd
Possible progeny? aaDd Albino with normal hearing

aaDd X aadd
Possible progeny? aaDd aadd Albino with normal hearing or Albino and deaf
Predicting progeny using Chi-square (x2) on Mendelian Ratios
• In genetics generally, a researcher is often confronted with results that are close
to but not identical with an expected ratio.
• But how close is enough?
• A statistical test is needed to check such ratios against expectations, and the chi-
square test fulfills this role.
• Chi-square test is useful in comparing observed results with those predicted by a
hypothesis.
• Null hypothesis: the observed numbers correspond to the expected ratio (1:1)
• Alternative hypothesis: the observed numbers do not correspond to the
expected ratio
Predicting progeny using Chi-square (x2) on Mendelian Ratios
• Assume we testcross the heterozygote Rr with RR.
• Based on the hypothesis, Mendel’s first law of equal segregation predicts that
we should have 50% Rr and 50% RR.
• Assume that in reality we obtain 120 progeny, and find that 55 are red and 65
are white. These numbers differ from the precise expectations, which would
have been 60 red and 60 white.
Predicting progeny using Chi-square on Mendelian Ratios
• The x2 value (0.84) value in the table of critical value of x2 will give the
probability value.
• The lines in the table represent different values of degrees of freedom (df).
The number of degrees of freedom is the number of independent variables
in the data minus 1.
• If the chi-square value that has P value higher than the cut-off value of
0.005 or 5%, we accept the null hypothesis, which is “the observed result is
not significantly different from the expected result’.
• The value below 5% is significantly different and the value below 1% is
highly significantly different. The values between 5% and 1% are n the
critical region of the chi-square distribution.
• We see that our x2 value of 0.84 lies somewhere between the columns
marked 0.5 and 0.1, in other words between 50% and 10%.
• This probability value is much greater than the cut-off value of 5%, so we
will accept the null hypothesis which states that the observed results is
compatible with the expected result.
Predicting progeny using Chi-square (x2) on Mendelian Ratios

• Therefore, 55 red and 65 white, which is observed data, are not significantly
different from 60 red and 60 white, which is the expected data.
 Human Genetic Disorders (Hereditary Diseases)

• Autosomal genetic disorders

• Autosomal dominant
• Autosomal recessive

• Sex-linked genetic disorders

• X-linked dominant
• X-linked recessive
• Y-linked
Pedigree Analysis
• A pedigree is a chart showing family relationships and the pattern of inheritance
of a particular trait.

Symbols used in human pedigree analysis

Pedigree analysis of autosomal recessive disorders
• Example is the human disease phenylketonuria (PKU)
• inherited as a recessive phenotype, with PKU determined by the allele p and
the normal condition by P.
• Therefore, sufferers from this disease are of genotype pp, and people who do
not have the disease are either PP or Pp.

Pp Pp

P~ pp pp P~

Phenotype Genotype
 Autosomal recessive
• Phenylketonuria (PKU)
• An inborn error of metabolism that results in decreased metabolism
of the amino acid phenylalalanine.
• Results from an inability to convert phenylalanine into tyrosine.
• Consequently, phenylalanine accumulates and is spontaneously
converted into a toxic compound, phenylpyruvic acid.
• Untreated PKU can lead to intellectual disability, seizures, behavioral
problems, and mental disorders.
• The treatment for PKU has been found out to be simply restricting
the dietary intake of phenylalanine in the affected individual. Many
PKU patients have benefited from this treatment.
 Autosomal recessive
• Phenylketonuria (PKU)
– caused by mutations at the
phenylhydroxylase (PAH) locus on
bands 12q22-24.1
– patients with PKU who are not
treated develop seizures and severe
psychologic problems, including
agoraphobia and other disorders,
have been reported
Pedigree analysis of autosomal recessive disorders

Pedigree of a rare recessive

phenotype determined by a
recessive allele a (and marriage
between cousins increasing
chance of affected individuals)
Pedigree analysis of autosomal recessive disorders

• The pedigrees of autosomal recessive disorders tend to look rather

rare, meaning, most people do not carry the abnormal allele.
• Furthermore, most of those people who do carry the abnormal
allele are heterozygous for it rather than homozygous.
• The formation of an affected person usually depends on the chance
union of unrelated heterozygotes.
• However, inbreeding (mating between relatives; marriage between
cousins) increases the chance that two heterozygotes will mate.
 Autosomal recessive

• Cystic Fibrosis
– Thick and viscous mucus in bronchial
tubes and pancreatic ducts resulting
in frequent lung infections
– caused by a mutation in the cystic
fibrosis transmembrane conductance
regulator (CFTR) gene found on
7q31.2

31
 Two copies of the
allele is needed to
cause the disease
http://www.nhlbi.nih.gov
 Autosomal recessive
• Tay-Sachs Disease
– progressive deterioration of psychomotor
functions
– the disease results from mutations on
chromosome 15 in the HEXA gene
encoding the alpha-subunit of the
lysosomal enzyme beta-N-
acetylhexosaminidase A
– harmful quantities of a fatty acid
derivative called a ganglioside accumulate
in the nerve cells of the brain
 Autosomal recessive
• Tay-Sachs Disease
– progressive deterioration of psychomotor
functions
– the disease results from mutations on
chromosome 15 in the HEXA gene
encoding the alpha-subunit of the
lysosomal enzyme beta-N-
acetylhexosaminidase A
– harmful quantities of a fatty acid
derivative called a ganglioside accumulate
in the nerve cells of the brain
Pedigree analysis of autosomal dominant disorders
• Here the normal allele is recessive, and the
abnormal allele is dominant.
• An example is pseudoachondroplasia, a type
of dwarfism.

The human pseudoachondroplasia

phenotype, illustrated by a family
of five sisters and two brothers
Pedigree analysis of autosomal dominant disorders
• Pseudoachondroplasia is a rare domninant
phenotype
• People with normal stature are
genotypically dd, and the dwarf
phenotype in principle could be Dd or DD.
• However, it is believed that the two
“doses” of the D allele in the DD genotype
produce such a severe effect that this
genotype is lethal.
• If this is true, all dwarf individuals are
heterozygotes.
Pedigree analysis of autosomal dominant disorders

Pedigree of a dominant
phenotype determined by
a dominant allele A
Pedigree analysis of autosomal dominant disorders

Polydactyly, a dominant phenotype

characterized by extra fingers, toes, or
both, determined by an allele P.
The numbers indicate the number
of fingers in the upper lines and the
number of toes in the lower.
Pedigree analysis of autosomal dominant disorders

Piebald spotting
 Autosomal dominant
• Huntington Disease
– neurological disorder
– caused by a trinucleotide repeat
expansion (CAG) in the Huntingtin
(Htt) gene on 4p16.3
– progressive degeneration of brain
cells
• Severe muscle spasms
• Personality disorders

One copy of the allele is

enough to cause the disease
Pedigree analysis of autosomal polymorphisms
• Polymorphism
• The coexistence of two or more common phenotypes of a character in a
population.
• The alternative phenotypes of polymorphisms are often inherited as alleles of
a single autosomal gene.
• In humans, examples include the dimorphisms brown versus blue eyes, dark
versus blonde hair, chin dimples versus none, widow’s peak versus none, and
attached versus free earlobes.
• Mutations in a gene that are passed on to the
offspring and that coexist with the original
gene result in polymorphisms
• Polymorphism in ground Sonora snakes and
Heliconius butterflies
Other Inheritance Patterns

Pleiotropy

One gene control several traits

Cell proliferation gene
Other Inheritance Patterns
Gene X
Polygenic Gene Y Trait 1
Several genes control one trait Gene Z

Height and color in Human Beings

45
Sex chromosomes and sex-linked inheritance

Chromosomal Determination of Sex in Drosophila and Humans

Sex-linked pattern of inheritance
• In humans, the X chromosome contains
many hundreds of genes; most of these
genes are not involved in sexual function,
and most have no counterparts on the Y.
• The Y chromosome contains only a few
dozen genes. Some of these genes have
counterparts on the X, but some do not.
• Most of the latter type are involved in
male sexual function, e.g. SRY gene
determines maleness of the individual.
• Several other genes are specific for
sperm production in males.
• SRY gene (sex-determining region Y)
Sex-linked pattern of inheritance
• A gene that is sex-linked (x-linked or y-
linked) shows patterns of inheritance
related to sex.
• Pseudoautosomal regions of the x and y
chromosomes are responsible for the
recognition of the two chromosomes during
crossing-over in meiosis.
 Other Inheritance Patterns

Sex-Linked
The gene is located in the sex chromosome (allosome)
X-linked gene

Dominant: Phenotype is seen in males & females if gene XA is present

Recessive: Phenotype is seen in female if homozygous for gene Xa; Phenotype is seen in
male if gene Xa is present
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
X-linked inheritance
• The eye color example concerned a
recessive abnormal allele, which must
have originally arisen by mutation.
• Wild type is a recessive allele
represented as w, while the normal
type is a dominant allele represented
as W.
• Red-eye is represented as w+ while Red-eyed and white-eyed wild type Drosophila
white eye is represented as w.
X-linked inheritance
• Note that in Drosophila, eye color
has nothing to do with sex
determination, so we see that genes
on the sex chromosomes are not
necessarily related to sexual
function.
• The same is true in humans:
pedigree analysis has revealed many
X-linked genes, yet few are related
to sexual function.
X-linked inheritance

Reciprocal crosses between red-

eyed (red) and white-eyed
(white) Drosophila give different
results
Pedigree analysis of x-linked recessive disorders
Important features
• Many more males than females show the rare
phenotype under study. This is because of the
product law: a female will show the phenotype
only if both her mother and her father bear
the allele (for example, XA Xa x Xa Y), whereas a
male can show the phenotype when only the
mother carries the allele. If the recessive allele
is very rare, almost all persons showing the
phenotype are male.
• None of the offspring of an affected male show
the phenotype, but all his daughters are
“carriers,” who bear the recessive allele
masked in the heterozygous condition. Half the
sons of these carrier daughters show the
phenotype.
Pedigree analysis of x-linked recessive disorders
Important features
• None of the sons of an affected male show the
phenotype under study, nor will they pass the condition
to their offspring. The reason behind this lack of male-
to-male transmission is that a son obtains his Y
chromosome from his father, so he cannot normally
inherit the father’s X chromosome, too.
Pedigree analysis of x-linked recessive disorders
• Red-green colorblindness is perhaps the most
familiar example of X-linked recessive
inheritance.
• People with this condition are unable to
distinguish red from green.
• The genes for color vision have been
characterized at the molecular level.
• Color vision is based on three different kinds of
cone cells in the retina, each sensitive to red,
green, or blue wavelengths.
• The genetic determinants for the red and green
cone cells are on the X chromosome.
• As with any X-linked recessive, there are many
more males with the phenotype than females.
Red-Green Colorblindness Chart
 The inheritance of the X-linked recessive condition hemophilia in the royal families of Europe

• Hemophilia, the failure of blood to clot, is another familiar example.

• Many proteins act in sequence to make blood clot. The most common type of hemophilia is
caused by the absence or malfunction of one of these proteins, called factor VIII.
• The most well known cases of hemophilia are found in the pedigree of interrelated royal
families in Europe.
Four siblings with testicular
feminization syndrome (congenital
insensitivity to androgens)
• People afflicted with
testicular feminization
syndrome are chromosomally
males, having 44 autosomes
plus an X and a Y, but they
develop as females.
• Has a frequency of about 1 in
65,000 male births.
• They have female external
genitalia, a blind vagina, and
no uterus.
• Testes may be present either
in the labia or in the
abdomen; sterile.
 X-Linked Recessive

Lubag Syndrome
– X-linked dystonia parkinsonism
(XDP)
– adult-onset, progressive,
debilitating movement disorder
unique to adult men with ancestry
from Panay
– result from a mutation of the TAF1
(TATA-binding protein-associated
factor 1) gene at Xq13.1

Rosales RL. Journal of Movement Disorders (2010)3:32-38. J Clin Pathol:Mol Pathol 2001;54:362–368
Pedigree analysis of x-linked dominant disorders
These disorders have the following characteristics
• Affected males pass the condition to all their
daughters but to none of their sons
• Affected heterozygous females married to
unaffected males pass the condition to half their
sons and daughters.
• All the daughters of a male
expressing an X-linked dominant
phenotype will show the
phenotype.
• Females heterozygous for an X-
linked dominant allele will pass the
condition on to half their sons and
daughters.
Y-linked inheritance
• Genes for such trait exclusive in human Y chromosome, with fathers transmitting
the genes to their sons.
• The gene that plays a primary role in maleness is the SRY gene.
Other Inheritance Patterns

Sex-Linked

Y-linked gene
Father’s phenotype will
pass onto male
offspring
Y-linked inheritance

Hairy ear rims

Other Inheritance Patterns

Sex-Influenced
The gene is located in the autosome (any chromosome other
than sex chromosomes) but traits are affected by sex

AA AA
Bald
Aa Aa
aa aa Bald

Males Females
Other Inheritance Patterns

Sex-limited
• Gene is present in both sexes of
sexually reproducing species but
are expressed in only one sex
and remain 'turned off' in the
other.
• E.g. milk production, breast
development, high-pitched voice
limited to females; presence of
beard, presence of Adam’s apple
limited to males
Lab Exercises
• Probability
• Chi-square Test