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