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Inheritance Patterns and Human GeneticsChapter 12

+Chromosomes and Inheritance

Francis Collins and his lab group discovered the gene responsible for cystic fibrosis (CF). Cystic fibrosis often is a fatal genetic disorder. Thick, sticky mucus builds up and blocks ducts in the pancreas and intestines and causes difficulty in breathing. In this chapter, you will learn how diseases, such as CF, and characteristics, such as eye color, are inherited and expressed.

+ Chromosomes

! Jeff Pinard worked in Collins’s lab

! He had CF

! Collins’s group was able to study CF gene partly because of work done by geneticists in early 1900s

+ Early Work

! Thomas Hunt Morgan began experimenting with fruit fly, Drosophila melanogaster

! He observed flies has 4 pairs of chromosomes

! Three pairs were identical in males and females

! One pair differed in size and shape

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! In females, 4th pair had 2 identical chromosomes (X)

! In males, they had X and one shorter one (Y)

! Today, geneticists call X and Y the sex chromosomes

+ Sex Chromosomes and Autosomes

! Sex chromosomes contain genes that determine sex (gender) of individual

! Remaining chromosomes not directly involved with gender are autosomes

! Humans, like flies – female XX, male XY

! Some organisms (i.e. chickens and moths) males have two identical sex chromosomes, females have two different ones

! Most plants, some fish – no sex chromosomes

+ Sex Determination

! Like other homologous chromosomes, sex chromosomes pair during meiosis

! As meiosis proceeds, paired chromosomes separate and move to different cells

! This means sperm cells have equal chance to receive X OR Y

! Each egg receives one X

! Each egg and sperm get one copy of each autosome

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! In mammals, when egg that carries X is fertilized by sperm carrying Y – result in male

! When egg fertilized by X sperm – female

! In male mammal, Y contains gene called SRY (sex-determining region Y)

! Codes for protein that causes gonads of embryo to develop as testes

! Because X doesn’t have SRY, gonads become ovaries

+ Effects of Gene Location

! During Morgan’s experiments with Drosophila, one scientist noticed that single male fruit fly had white eyes instead of normal red eyes

! Morgan crossed white eyed male with red eyes female

! All F1 was red eyed

! Therefore, red eyes were dominant

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! Then he crossed F1 males with F1 females

! What were the resulting percentages of white and red eyed flies?

! 3:1 red:white

! BUT all white eyed flies were male

+ Sex-linked Genes and Traits

! Morgan hypothesized that gene for eye color carried on X chromosome and Y chromosome doesn’t have allele for eye color

! XR is red Xr is white

! Cross XRXR female with XrY male " all F1 females with be XRXr and all F1 males will be XRY

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! In F2 generation, half females will be XRXR, half XRXr

! All red eyes

! In F2 males, half will be XRY, half will be XrY

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! Results show genes reside on chromosomes and red eye color gene is on X

! Morgan called these X-linked genes

! Genes like SRY are Y-linked genes

! Sex-linked trait refers to trait that is coded for by allele on sex chromosome

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! X chromosome larger than Y, so has more genes

! Most X-linked traits have no homologue on Y chromosome

! b/c males have only one X, a male with recessive X-linked trait will exhibit that trait

+ Linked Genes

! Morgan and others hypothesized that if genes are inherited together is because they are on the same chromosome

! He studied two fly genes – body color and wing length – located on same autosome

! Gray body (G) Black body (g)

! Long wings (L) short wings (l)

+! Morgan crossed

! All F1 had GgLl

GGLL flies with ggll flies

+! Then he crossed two F1

! Flies in F2 were 3 gray long wing to 1 black short wing

! If alleles were on different chromosomes they would sort independently and produced 9:3:3:1, like Mendel’s peas

! Morgan called pairs of genes that tend to be inherited together linked genes

! A set of linked genes are a linkage group

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! He hypothesized genes are linked b/c they are found on same chromosome

! His F2 crosses produced a few offspring unlike either parent

! Gray short wings (Ggll) and black long wings (ggLl)

! Morgan realized that mutations are too rare to explain these unexpected results

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! He inferred that crossing-over must be responsible

! During the first division of meiosis, crossing-over does not create new genes or delete old ones

! It rearranges allele combinations

+ Chromosome Mapping

! The farther apart two genes are on chromosome, the more likely a cross-over will happen

! Greater % of F2 showing recombinant traits, the farther apart the genes for those traits must lie on chromosome

! Researchers do breeding experiments and use results to prepare chromosome map

! Chromosome map " diagram that shows linear order of genes on a chromosome

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! % of crossing-over for two traits is proportional to distance between them on chromosome

! Map unit " frequency of crossing-over of 1%

+ Mutations

! CF results from mutation

! Mutation is a change in nucleotide base sequence of gene or DNA molecule

! Germ-cell mutations happen in gametes! Do not affect organism itself! Can be passed to offspring

! Somatic-cell mutations happen in body cells! Can affect organism! Cannot be inherited! Ex. Types of human skin cancer, leukemia

! Lethal mutation causes death, often before birth

+ Beneficial mutations

! Some mutations result in phenotypes that benefit individual

! Better chance of surviving and reproducing

! Have evolutionary advantage

+ Chromosome mutations

! Involve changes in structure of chromosome or loss or gain of chromosome

1. Deletion " loss of a piece of chromosome due to breakage

2. Inversion " segment breaks off, flips around, reattaches

3. Translocation " piece breaks off and reattaches to nonhomologous chromosome

4. Nondisjunction " chromosome fails to separate from homologue during meiosis1. One gamete gets extra copy2. Other gamete gets no copy3. Ex. Down syndrome

+ Gene mutations

! Change in single nucleotide called point mutation in single gene

! Substitution " one nucleotide replaces another! If in codon, amino acid can be changed

! Deletion " one or more nucleotides is lost! Can cause incorrect grouping of remaining codons! Called frameshift mutation! Causes all amino acids after change

! Insertion " one or more nucleotides are added to gene! Can also result in frameshift mutation

+Human Genetics

This section investigates how geneticists analyze genetic data from families to track the inheritance of human genes. It also explores the genetic and environmental factors that influence human genetic traits and disorders, and discusses how geneticists detect and treat human genetic disorders.

+ Inheritance of Traits! Geneticists can study human traits and trace

genetic diseases from one generation to the next by studying the phenotypes of family members in a pedigree

+ Pedigrees

! Diagram that shows how a trait is inherited over several generations

! Squares stand for males

! Circles for females

! Filled means person has that trait or condition

! Empty means person does not have trait or condition

! Horizontal lines connect mates

! Vertical lines indicate offspring left to right in order of birth

! Roman numerals indicate generation

+ Patterns of Inheritance

! We learn about genetic diseases by analyzing patterns of inheritance – expression of genes over generations

! Pedigrees help interpret patterns of inheritance

! Ex. If trait is sex-linked, usually seen only in males

! Most sex-linked traits are recessive

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! If trait is autosomal dominant everyone with the trait will have a parent with the trait

! If recessive, individual with trait can have one, two or neither parent exhibit the trait

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! If individuals with autosomal traits are homozygous dominant or heterozygous, their phenotype will show dominant characteristic

! If homozygous recessive, phenotype will show recessive characteristic

! Two people who are heterozygous carriers of recessive mutation will not show mutation! Can produce children who are homozygous for recessive allele! Children will show recessive phenotype

+ Genetic traits and disorders

! Genes controlling human traits show many patterns of inheritance

! Some of these cause genetic disorders

! Genetic disorders are diseases or disabling conditions that have genetic basis

+ Polygenic inheritance

! Most human characteristics are polygenic " influenced by several genes

! Show many degrees of variation

! Skin color results from additive effects of 3-6 genes! Control amount of melanin in skin! More melanin – darker skin

! each of the 3-6 genes has allele that makes love amounts of melanin and another allele that makes high amounts of melanin

! Final amount of melanin comes from number of high-melanin alleles

! Eye color, height, hair color also polygenic

+ Complex Characters

! Characters that are influenced by environment AND genes

! Skin color is polygenic and complex

! Exposure to sunlight causes skin to become darker no matter what genotype is

! Height also affected by genes AND nutrition and disease! NOT swimming or basketball or medicine, etc.

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! Marie-Claire King studied genetics of breast cancer in families where individuals with disease had it at younger ages than average patient

+! In Family A, each affect person has affected parent

! This is inheritance pattern of dominant trait

! Family B shows genetic and environmental factors can influence whether person expresses a trait

! Female III-A does not have breast cancer but has child that develops breast cancer

! III-B in family B is male with breast cancer

+ Multiple Alleles

! Many genes have more than 3 alleles

! In humans the ABO blood groups are controlled by alleles IA, IB, and I

! IA and IB are codominant

! I is recessive

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! IA and IB encode variants of enzyme that cause two different sugar molecules to appear on surface of RBC

! i allele doesn’t have any enzyme activity, so neither sugar is on RBC

+ Incomplete Dominance

! Individual displays trait that is intermediate (between) two parents

! Ex. Some people have mutation that prevents removal of cholesterol from body

! Leads to high blood-lipid levels and possible premature heart disease

! Child who has one parent with and one without mutation will have moderate increase in blood lipids

+ X-Linked Traits

! Pedigree usually reveals many affected males and no affected females

! Male inherits x-linked trait from mother

! Colorblindness is recessive x-linked disorder where individual cannot distinguish certain colors like red and green

! several x-linked genes encode proteins that absorb red or green light in eye

! Mutation disrupts genes so eye cannot absorb some colors of light

! Doctors test using charts

+ Sex-influenced traits

! Involved in other complex characters

! Males and females can show different phenotypes even when they have same genotype

! Usually autosomal

! Ex. Allele dominant in males but recessive in females controls patter baldness (found in men)

! Difference due to higher levels of testosterone

! Testosterone interacts with genotype to produce pattern baldness

+ Single-Allele Traits

! Geneticists have discovered more than 200 human traits controlled by single dominant allele

! Huntington’s disease (HD) is autosomal dominant condition characterized by forgetfulness and irritability

! Develops as person reaches 30-40 years of age

! Progresses to muscle spasms, severe mental illness, then death

! Because dominant gene exists in every HD heterozygote, each affected person has at least one affected parent

! Many patients have already had children by the time symptoms appear

! Direct DNA testing beginning to allow earlier diagnosis

+ Detecting Genetic Disease

! Genetic screening is examination of person’s genetic makeup

! May involve karyotypes, blood tests for certain proteins, or direct DNA testing

! Doctors can detect more than 200 genetic disorders in fetus

! Amniocentesis allows doctor to remove some amniotic fluid between week 14-16

! Geneticists analyze fetal cells for genetic disease by looking at chromosomes and proteins in fluid

+ Chorionic Villi Sampling

! Doctor takes sample of chorionic villi – cells made from zygote that grow between mother’s uterus and placenta – between week 8-10

+ Genetic Counseling

! Process of informing a person or couple about their genetic makeup

! Form of medical guidance that informs people about problems that might affect their offspring

! Studying data from genetic screening tests and pedigrees allow genetic counselor to predict likelihood of affected child

! For diseases with environmental and genetic factors, doctors and counselors can advise families on how to lower risks

+ Treating Genetic Disease

! Many ways to treat genetic disease

! Some just treating symptoms

! Ex. Phenylketonuria (PKU) lacks an enzyme that converts amino acid phenylalanine into amino acid tyrosine

! Phenylalanine builds up in body and causes mental retardation

! Doctors prescribe strict food routines to eliminate phenylalanine from diet

! PKU detected by blood test during first few days of life

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! For CF patients, doctors prescribe 45 minute sessions of pounding on the back and chest to loosen mucus

! Sometimes doctors can use symptom-prevention methods

! Ex. Insulin injections for diabetes

! Hemophilia – injections of blood-clotting proteins

+ Gene Therapy

! Replacing defective gene

! Technique that places healthy copy of gene into cells where gene is defective

! Relies on knowing gene sequences

! Healthy gene sequence inserted into DNA of virus

! Can introduce modified virus into lungs

! Virus infects cells and brings functional gene with it

! Improves symptoms until infected cells slough off

! Patient must have procedure again

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! Where only body cells are altered is called somatic cell gene therapy

! Germ cell gene therapy attempts to alter eggs and sperm

! Somatic cell gene therapy is thought to be extension of normal medicine

! Germ cell gene therapy is riskier and also has ethical issues associated with it because future generations can be affected in unpredictable ways