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Principles of Inheritance
GENETICS
DNA• found in nucleus of each cell• composes chromosomes• chromosomes contain genes• genes-biological blueprints• dictate how we look, how our
body functions & may be even how we behave
• traits are inherited • passed down from
generations before us• science of heredity-genetics
Genetics• modern science of genetics-began
1860• Gregor Mendel• Father of Genetics• helped lay down principles of
modern genetics• Central European monk• conducted experiments using
garden peas• ideas were published in 1860's• unrecognized until after his death • not appreciated until early 1900s• work applies to humans as well as
peas• illustrates basic rules of
inheritance
Rules of Inheritance• Mendel discovered
basic genetic principles breeding garden pea plant
• exercised strict control over mating of these plants
• studied seven characteristics
• each with two possible forms
Rules of Inheritance• most important conclusion:
inherited variations are transmitted to offspring as discrete units
• until this time most assumed characteristics of individual organisms were blended from generation to generation
• particulate theory• Particles-now known as
genes
GENE
True Breeding Plants• before beginning
Mendel worked with his plants to ensure he had true-breeding plants
• produce offspring that are identical to parents
• purple flowers purple offspring
Hybridization-Cross-Breeding
• purple mom + white dad
• hybridization
• or simply-cross
• offspring are hybrids
Cross-Breeding• true breeding parents-
P generation–for parental
• children-F1 generation–f=filial-Latin for son
• when F1 plants are matedoffspring-F2 generation
Mendel’s Experiments• Mendel noticed that traits were
transmitted in predictable ways from parents to offspring
• crossed different strains of purebred plants & studied their progeny
• at first worked with consequences of crossing one trait at a time
• monohybrid cross• would cross purple plant with
white plant & look at color of offspring
• F1 generation-always purple• Mendel wondered what had
happened to heritable factor for white
Mendel’s Experiments• when crossed F1
generations
• missing white factor reappeared
• 75% of offspring had purple flowers
• 25% had white flowers
• 3:1 ratio
Mendel’s Experiments• same pattern of
inheritance was found for all characteristics of pea plant
• in cross-pollinating green pods-first offspring generation (f1) always had green pods
• f2 generation consistently had 3:1 ratio of green to yellow
Mendel’s Conclusions• white or yellow genes do not
disappear in f1 generation• masked by purple or green
gene• individuals inherit one unit
from each parent for each trait
• specific trait may not show up in an individual
• may be passed to next generation
• from his results, Mendel described four specific hypotheses
Mendel’s Hypotheses• there are alternative
forms of genes-alleles• for each inherited
characteristic an organism must have 2 genes– one from each parent
• maybe-same or different
• two of same allele- homozygous
• two different alleles-heterozygous
Mendel’s Hypotheses• alleles represent genotype• when alleles are differentallele
that determines appearance (phenotype) is dominant
• other allele has no observable effect on phenotype-recessive
• dominant genes-always expressed
• need only one dominant gene to have particular phenotype
• to have recessive characteristic- must carry two recessive genes– unless gene is located on
sex chromosome• customary to use capital letters
for dominant traits• small letters for recessive ones
Genotype & Phenotype• brown eye color is
dominant (B)
• blue (b) is recessive
• person with genotype BB or Bb would have brown eyes
• person with genotype bb would have blue ones
Law of Segregation• each f1 generation plant
inherits one allele from one parent & one allele from other
• when f1 plants mated, each allele had equal chance of being passed on to offspring
• for any particular trait, pair of alleles from each parent separate
• only one allele passes from each parent to offspring
• which allele in parent's pair is inherited is-chance
Law of Segregation• genes occur in pairs because
chromosomes occur in pairs• during gamete production-
members of each gene pair separate so each gamete contains one member of a pair
• during fertilization full number of chromosomes is restored
• members of a gene or allele pair are reunited
• segregation of alleles occurs during process of gamete formation-meiosis
Punnett Square• used to illustrate basic
rules of inheritance• shows alleles of mother
and alleles of father• by simple multiplication
one can figure out probability of obtaining offspring with characteristics of parents
Punnett Square
Examples
Example
• Brown eyed father-BB• Blue eyes-mother-bb• Recessive trait
Example• father with red hair• recessive trait• has children with mother with
black hair• dominant trait• probability of having children
with red hair is• ?• each child would carry a gene
for red hair• this is the case if mother has
two dominant alleles in her genotype
• what if we know that woman’s mother had red hair
r r
R
R
Rr Rr
RrRr
Dihybrid Cross• Mendel next
crossed & followed inheritance of two traits at same time
• dihybird crosses
Dihydrid Crosses• two characteristics Mendel
studied were seed shape & color
• seeds were either green or yellow & either wrinkled or round
• knew round & yellow were dominant
• wrinkled & green were recessive
• wondered what would happen in a dihybrid cross
• mating GGWW pea with ggww one
Principle of Independent Assortment
• f1 generation yielded heterozygous hybrids or RrYy
• phenotype was round & yellow• when f1 generation was crossed found
distribution of one pair of alleles into gametes did not influence distribution of other pair
• genes controlling different traits are inherited independently of one another
• Principle of Independent Assortment
• ratio was 9:3:3:1• 9 yellow, round, 3 green, round, 3
yellow, wrinkled and one completely recessive pea or green, wrinkled
Punnett Square
Test Crosses• used to determine genotype of
specific specimens• have a purple flowering pea plant• want to know if pea plant has
purple flowers because it is homozygous or heterozygous
• unknown plant is mated with known plant
• cross purple-flowered unknown with white-flowered plant (completely recessive)
• if all offspring exhibited purple flowersconclude unknown parent is homozygous
• if offspring exhibited 1:1 ratio of purple to white flowersconclude unknown parent is heterozygous
Mendelian Pattern Inheritance• genes coding for a particular trait are
located at particular positions on chromosomes-loci
• come in several forms-alleles• receive one allele from each parent• if identical-homozygous for a trait• if different-heterozygous• recessive traits are not expressed in
heterozygotes• for recessive alleles to be expressed,
one must have 2 copies• dominant traits can be expressed in
presence of another, different allele• dominant alleles prevent expression or
mask recessive alleles in heterozygotes.
• traits that are result of one set of genes are single gene traits
• transmission of single gene traits follows Mendel’s patterns of inheritance
Other Patterns of Inheritance
• over 4,500 human trains are inherited according to simple Mendelian principles
• there are exceptions to Mendel’s rules
Incomplete dominance• offspring is heterozygous
for a trait but phenotype is intermediate between phenotypes of homozygous parents
• heterozygous snapdragons of white & red parents have pink flowers
• sickle cell disorder • homozygous individuals
have either normal blood or sickle cell anemia
• heterozygous individuals have sickle cell trait
Incomplete Dominance
Codominance• phenotypes for both alleles at
a locus are expressed at same time
• human ABO blood system shows both simple Mendelian inheritance & codominance
• A & B alleles are dominant to O
• if have genotype AOblood type is A
• if BOblood type is B• however, neither A or B alleles
are dominant to one another• codominant-both traits are
expressed• person with allele for A & one
for B has blood type AB
• OO = Blood type OAO = Blood type ABO = Blood type BAB = Blood type ABAA = Blood type ABB = Blood type B
Polygenetic Inheritance• characteristics due to
multiple alleles • many genes define a trait• Height• combination of genes for
height of face, size of vertebrate & length of leg bones
• skin color-due to interactions between at least 3 pairs of alleles
• continuous traits• show gradations• there is a series of
measurable intermediate forms between 2 extremes
Sex-Linked Genes• characteristics found
on X & Y chromosome• inherited differently• X linked, recessive
shows effect more in males
• Recessive– no corresponding
gene on Y chromosome
– therefore trait will be expressed
Chromosomes• every nucleus in every
somatic or body cell carries genetic blueprint for who we are
• 46 chromosomes• each paired with a like
chromosome• 23 pairs• 23 chromosomes came
from our mothers• 23 from our fathers
Sex Chromosomes• exception found
with sex chromosomes
• X& Y chromosomes
• other 22 pairs are autosomes
• sex chromosomes determine gender
• XX = girl & XY = boy
Sex-Linked Traits• sex linkage
– results from action of genes present on sex chromosomes
• most located on X chromosome• nearly all are recessive• most X-linked genes have no
homologous loci on Y chromosome
• baldness, color blindness & hemophilia
• occur more in males than females• males receive only one allele of a
gene located on X chromosome• therefore even recessive alleles
will be expressed in males• there is no dominant gene to
mask it
Inheritance of Sex-Linked Genes• for sex linked traits-females are carriers • if have one recessive allele• affected when possess 2 recessive
alleles• affected fathers pass X-linked allele to
all daughters but not to sons• males receive X chromosomes only
from mothers• mothers can pass sex-linked alleles to
both sons & daughters• unaffected males do not carry defective
gene• carrier female has 50% chance of
producing affected son• 50% chance of producing carrier
daughter• affected females are homozygous-rare• condition requires both carrier mom
and father with the condition
Genetic Disorders• can be inherited as dominant or recessive traits by simple
Mendelian principles• dominant disorders-inherited when one copy of dominant
allele is present• recessive disorders require presence of two copies of
recessive gene• disorders may be present at birth or become evident later
in life• most inherited from parents• 15-20% are result of new mutations
– molecular alterations in genetic material, arising during fetal development
• disorders are classified according to location of defective gene-autosomal or sex & mode of transmission-dominant or recessive
Autosomal Genetic Disorders• each human has 22 pairs of
homologous autosomal chromosomes
• 1 set of sex chromosomes– females-homozygous-XX – males-heterozygous-XY
• more than 10,000 single gene disorders have been catalogued
• autosomal disorders are found in 1 in 500 individuals in general population
• affect males & females equally
Autosomal Recessive & Dominant Disorders
• autosomal recessive disorders – require 2 recessive genes
for particular problem• autosomal dominant
disorders– require individual has at
least one dominant allele• for autosomal dominant
disorders at least one parent must be affected
• for autosomal recessive disorders parents may or may not have the disorder
• parents without disorder are called carriers
Autosomal Dominant Disorders • few in number• close to 4,400 known• dominant genes often
code for functional or structural proteins– typically affect body
structures such as skin, bone, and teeth
• everyone bearing gene is affected
• Huntington's disease– causes slow
progressive deterioration of brain & eventually death
Paternal gametes
D d
d
d
Maternalgametes
D = mutant gened = normal gene
Dd dd
Dd dd
2 dd: 2 Dd
Autosomal Dominant Disorders• expressed in those who have one
altered copy of a gene• parent has 1 in 2 chance of passing
altered gene to offspring with each pregnancy
• risk remains constant no matter how many affected or unaffected children are born
• follows predictable patterns of inheritance
• males & females-equally affected• affected individual has an affected
parent• unaffected individuals do not
transmit disorder• offspring of affected person mating
with a normal mate has 50% change of inheriting disorder
• rare mating of 2 individuals each with one copy of defective gene has a 75% chance of producing an affected offspring
Autosomal Dominant Diseases• Brachydactyly
– short fingers & toes• familial hypercholesterolemia, • familial polycystic disease• one type of Alzheimer's disease• hereditary colon cancer• Achondroplasia
– dwarfism in which homozygous condition is lethal at embryo stage
Autosomal Recessive Disorders• due to recessive allele• manifested only in
homozygous genotype• person having
heterozygous genotype-Aa is a carrier
• estimated-each carry 5-10 recessive lethal genes
• most never experienced because have another chromosome with good copy of gene from other parent
• recessive defective genes when present in only one copy do not affect owner
Autosomal Recessive Disorders• males & females-equally
affected• disorder-not apparent in
parents or relatives• if individual is affected-
both parents must be carriers
• mating of 2 carriers produces 25% chance of producing offspring with disorder
• 50% of offspring will be a carrier for the disorder
Autosomal Recessive Disorders • recessive
conditions that affect humans include
• cystic fibrosis• Tay-Sachs
disease• beta thalassemia• phenylketonuria• albinism
Albinism• group of inherited
conditions in which there is little or no pigment in eyes, skin, and hair
• individuals have inherited two altered copies of a gene that does not work correctly
• does not allow body to make usual amount of melanin
• result of lack of tyrosinase• enzyme that catalyzes
formation of melanin from tyrosine
Cystic Fibrosis• most frequent &
common single gene disorder
• 5% of white Americans carry defective gene
• 1 in 25 persons of European ancestry are carriers
Sex Linked Genetic Disorders• more males than
women affected
• need to acquire only one recessive trait from mother
• due to gene on X chromosome
Sex linked Disorders
Hemophilia
Diagnosis • ability to diagnosis improved over last few years• ability to detect exceeds ability to treat• many children with recessive disorders are born to parents
who are normal• possible to do carrier testing to determine whether or not
someone is a carrier for a particular recessive gene• by determining whether individual is a carrier risks for
passing gene to an offspring can be assessed• carrier testing may be considered by individuals who have
family history and/or are members of an ethnic group known to be at increased risk for a disorder
• Genetic counseling is often recommended prior to carrier testing
Fetal Testing• techniques are available to test fetus prior to
birth• Ultra sound• non invasive • uses sound waves to produce image of fetus• used to determine gestational age, fetal position
& placenta location• cannot detect biochemical or chromosomal
abnormalities.• Amniocentesis• invasion • needle inserted into abdomen or vaginafluid is
obtainedskin cells of fetus are cultured & harvested & analyzed for abnormal levels of certain substances
• karyotype can be performed on harvested cells indicating chromosomes present
• only certain disorders can be detected this way• may not provide information until late in
pregnancy
Amniocentesis
Fetal Testing• Chorionic Villus Sampling • tissue removed from chorion
– outer membrane of fetal sac• can do as early as 8 weeks of gestation• cells do not need to be cultured• Blood tests• conducted on mother• 15 to 20 week of pregnancy• Alpha fetoprotein (AFP) in mother’s blood
may indicate neural tube defects • Embryoscopy
– direct visualization• can be used to detect abnormalities & to
treat them• can be conducted as early as 1st trimester• scope is inserted into uterus• often used to diagnose structural
abnormalities• may be used to treat disorders with gene
or stem cell therapy