Inheritance Patterns & Human Genetics

Sex chromosomes form pairs and segregate during meiosis I just like the 22 autosomes

In mammals and most insects, males are XY and females are XX

(Also XX/X0 system, ZW system, haploploidy and non-genetic systems)

Leads to 50/50 chance male or females

Sex Linkage

Presence of a gene on a sex chromosome

X-linked or Y-linked (X is larger so has more)

Eye color in Drosophila an example:

Cross red eyed female with a white eyed male

All F1 red eyed flies

F2 showed 3:1 ratio expected, but white eyed flies were all male

Gene Linkage

Morgan’s research on fruit flies led him to principle of linkage

Identified over 50 Drosophila genes

Discovered many seemed “linked” in a way that violated independent assortment

Ex.- reddish-orange eyes and miniature wings inherited together

Observed so many linked genes, Morgan could group them into 4 linkage groups

Linkage groups assorted independently, but all genes in 1 group inherited together

Drosophila has 4 linkage groups

Also has 4 chromosomes

Two conclusions:

-each chromosome is a group of linked genes

-principle of independent assortment still holds true

Chromosomes assort independently, not individual genes

Gene Maps

Crossing-over sometimes separates and exchanges linked genes

Produces new combinations of alleles

Helps generate genetic diversity

Can use rates of crossing-over events in meiosis to produce a gene map

Shows relative distances between genes on a chromosome

Further apart two genes are, more likely they are to recombine (during crossing-over)

Closer together, the less likely they are to become “unlinked”

MutationsChanges in the genetic materialGerm-cell mutations occur in gametesSomatic mutations occur in body cellsLethal mutations cause death, often before

birthKinds of MutationsChanges in a single gene known as gene

mutationsChanges in a whole chromosome known as

chromosomal mutations

Gene Mutations

Mutation involving changes in one or a few nucleotides are called point mutations

Include:

Substitutions- one base changed to another

Insertions- extra base inserted

Deletions- base is removed from sequence

Substitutions usually only affect one amino acid in protein

Insertions/deletions can affect whole protein

Sequence read in codons (groups of 3)

If base added or deleted, “shifts” the codons that are read

Called frameshift mutations

May change every amino acid after mutation

DNA: TAC-GCA-TGG-AAT

mRNA: AUG-CGU-ACC-UUA

Amino acids: Met-Arg-Thr-Leu

Substitution

DNA: TAC-GTA-TGG-AAT

mRNA: AUG-CAU-ACC-UUA

Amino acids: Met-His-Thr-Leu

DNA: TAC-GCA-TGG-AAT

mRNA: AUG-CGU-ACC-UUA

Amino acids: Met-Arg-Thr-Leu

Insertion

DNA: TAT-CGC-ATG-GAA-T

mRNA: AUA-GCG-UAC-CUU-A

Amino acids: Ile-Ala-Tyr-Leu

DNA: TAC-GCA-TGG-AAT-GGA

mRNA: AUG-CGU-ACC-UUA-CCU

Amino acids: Met-Arg-Thr-Leu-Pro

Deletion

DNA: TGC-ATG-GAA-TGG-A

mRNA: ACG-UAC-CUU-ACC-U

Amino acids: Thr-Tyr-Leu-Thr

Chapter 14- Human Genome

Sickle Cell Anemia

Common genetic disorder found in African Americans

Have bent, twisted red blood cells

Cells more rigid, tend to get stuck in capillaries

Produces physical weakness and damage to brain, heart, and spleen

Chapter 14- Human Genome

Protein affected is hemoglobin:

Just one base change causes protein to be abnormal

Abnormal protein causes sickle shape of cells

Why so many African Americans?

Tropical regions have high prevalence of malaria

Chapter 14- Human Genome

People who are heterozygous normally healthy, and are resistant to malaria

Sickle cell allele is beneficial in these areas

A Mutation Story

Chromosomal Mutations

Involve changes in the number or structure of chromosomes

Can change locations of genes

Can change the # of copies of some genes

Mutations that cause dramatic changes in protein structure or gene activity often harmful

Mutations may produce proteins with new or altered activities that may be useful

Mutations in gametes can be passed along to offspring

Basis for new genetic variation in species

Studying Human Inheritance

Human genes inherited according to Mendel’s principles

Must identify an inherited trait is controlled by a single gene

First, must establish trait is inherited

Second, must study how trait is passed from generation to generation

Pedigree chart is used to show relationships within a family and follow a particular trait

Genetic counselors analyze pedigrees to infer the genotypes of family members

Only useful for single-gene traitsMany human traits are polygenicControlled by many genesMany traits also influenced by environmental

factors

Recessive Alleles

Many human genes become known through study of genetic disorders

Most cases, presence of a normal gene only revealed when abnormal allele affects phenotype

Autosomal recessive inheritance

Ex.- phenylketonuria (PKU)

Lack enzyme needed to breakdown phenylalanine

Can buildup in tissues in infants and cause mental retardation

Caused by autosomal recessive allele on chromosome 12

Dominant Alleles

If you have dominant allele for a genetic disorder, it will be expressed

Ex.-

Achondroplasia (form of dwarfism)

Huntington’s disease

Causes progressive loss of muscle control and mental function (begins in 30’s)

Autosomal dominant inheritance

Multiple phenotypes from multiple allelesMore common for multiple alleles to control a

trait in a populationOnly two alleles of a gene can exist within the

cell, multiple alleles for a single gene can be found within a population

Blood Group GenesHuman blood comes in variety of genetically

determined blood groupsNumber of genes responsible, best known are

ABO blood groups and Rh blood groups

Rh determined by single gene with two alleles

Either positive (dominant allele) or negative

ABO group more complicated

Three alleles: IA, IB, and i

IA & IB are codominant

Alleles produce proteins on red blood cell surface

i allele is recessive; no proteins produced

Polygenic Inheritance

Traits that are determined through expression of two or more genes

Polygenic traits show wide range of phenotypes

Ex- eye color, skin color, height

Sex-linked Traits

Traits controlled by genes found on the sex chromosomes

Any recessive allele found on the X chromosome of a male will not be masked (there is no other X in males)

X-linked dominant and Y-linked are very rare

Colorblindness

3 genes associated with color vision found on X chromosome

In males, defective version of any of these produces colorblindness

Most common form: red-green colorblindness; affects 1 in 10 males (U.S.)

Among females: 1 in 100

Males have only one X chromosome

So, all X-linked alleles are expressed in males (even if recessive)

In females, must have two copies of recessive allele to express trait

Pattern:

Males show recessive trait more often

Males pass along allele to daughters

Hemophilia

Two important genes on X chromosome help control blood clotting

Recessive allele in either may cause hemophilia (blood clotting protein missing)

1 in 10,000 males born with disorder (U.S.)

Treated by injections of clotting protein

Duchenne Muscular Dystrophy

Sex-linked disorder results in progressive weakening and loss of skeletal muscle

1 in 3000 males in U.S.

Caused by defective version of gene that codes for muscle protein

No treatment or cure to date

Chromosomal Disorders

Mechanisms that separate chromosomes in meiosis work well; sometimes fail

Most common error = nondisjunction

Occurs when homologous chromosomes fail to separate

Abnormal #’s of chromosomes in gametes may lead to genetic disorders

Down Syndrome

Individual may be born with 3 copies of a chromosome (called trisomy)

Most common form of trisomy is called Down Syndrome (Trisomy 21)

~1 in 800 born with Down Syndrome in U.S.

Produces mild to severe mental retardation

Detecting Human Disorders

Genetic screening or genetic counseling

-May use a karyotype or pedigree

Fetal cells obtained through an amniocentesis or chorionic villi sampling

Genetic tests have been developed to take advantage of small differences in DNA