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BIOL 133 Exam 4 Study Guide

Terms in this set (91)

Cancer
uncontrolled cell division
Carcinogens
substances that cause cancer by mutating DNA (radiation, chemicals, viruses)
Benign
tumor stays in one place and does not grow into surrounding tissue
Malignant
tumor is invasive and moves to other parts of the body
Metastasis
movement of cancer cells around the body
Cancer
alterations in genes - most cancers are NOT inherited (damage occurs during lifetime)
Oncogenes
when mutated/expressed at abnormally high levels converts cell into cancer cell
Tumor suppressor genes
genes whose products inhibit mitosis
Proto-oncogenes
genes that normally trigger cell division
- estimated that 1% of ~30,000 genes in human genome are proto-oncogenes
p53 gene
plays a role in either DNA repair or apoptosis
3 basic cellular pathways
- affected by cancer causing gene mutations
1. cell fate: differentiation
2. cell survival: oxygen availability and preventing apoptosis
3. genome maintenance: abilities to survive in the presence of reactive oxygen species and toxins
Loss of cell cycle control
- many types of cancer result from faulty check points
- timing, rate, and number of cell divisions depend on:
- protein growth factors
- signaling molecules from outside the cell
- transcription factors within the cell
Checkpoints control cell cycle
- a mutation in a gene that halts or slows the cell cycle can lift the constraint, leading to inappropriate mitosis
- failure to pause in order to repair DNA can allow a mutation in an oncogene or tumor suppressor gene to persist
Telomeres
- loss of control of telomere length may also contribute to cancer
- telomeres protect chromosomes from breaking
- gametes keep telomeres long using telomerase
Telomerase
- normal, specialized cells have telomerase turned off, limits cell division
- cancer cells turns telomerase back on
- telomeres extend, and releases the brake on rapid cell division
Tumors
- produce antigens recognized by immune system
- rapid development can overwhelm immune system
Sporadic cancers
- damage to SOMATIC cells
- occur sporadically in non-sex cells
- result from a single dominant mutation or two recessive mutations in same gene
- cancer susceptibility not passed on to offspring
Inherited cancers
- caused by damage to both germline cells & somatic cells
- susceptibility to cancer is inherited
- germline cancers are rare
- occur earlier in life than somatic cancers
Characteristics of cancer cells
- loss of cell cycle control
- less adherent
- heritable
- transplantable
- dedifferentiated
- lack contact inhibition
- induce local blood vessel formation
- invasive
- increased mutation rate
- can spread (metastasize)
A cancer cell may descend from
- a stem cell that yields slightly differentiated daughter cells that retain the capacity to self-renew
- a specialized cell that loses some of its features and can divide
Cancer stem cells
- produce both cancer cells and abnormal specialized cells
- found in brain, blood, and epithelium cancers
Cancer by loss of specialization
- specialized cells lose some of their distinguishing features as mutations occur when they divide
- cells may begin to express "stemness" genes that override signals to remain specialized
Driver mutation
provides the selective growth advantage to a cell that defines the cancerous state
- oncogenes or tumor suppressor genes which can be generated from abnormal chromosomes
Passenger mutation
- occurs in a cancer cell
- does not cause or propel the cancer's growth or spread
- occurs in cancerous and noncancerous cells
Driver mutation cumulative effect
"Gatekeeper" enables a normal epithelial cell to divide faster than others
- clone of faster-dividing cells gradually accumulates
- second mutation boosts division rate
Driver mutations can be identified by
- comparing mutations in tumor cells from people at different stages of the same cancer
- studying cancer cells of patients who respond to a drug then relapse
Environmental causes of cancer
- environmental factors contribute to cancer by mutating or altering the expression of genes that control the cell cycle, apoptosis, and DNA repair
- inheriting a susceptibility gene places a person farther along the road to cancer
- however, cancer can happen in somatic cells in anyone
- interactions between genes and environment exist
- environmental factors contribute to cancer by mutating genes and altering gene expression
Challenges of diagnosing and treating cancer
- ability to sequence cancer exomes and genomes is providing a new specificity for diagnosing and treating cancer
- cell-free tumor DNA (ctDNA) can reveal response to a treatment
- liquid biopsy - a less invasive method to monitor cancer's spread
- genetic information helps physicians choose appropriate drugs by stratifying patients
Biotechnology
use or alteration of cells or biomolecules for specific purposes
Transgenic organisms
organism with DNA from another species
Recombinant DNA
adding foreign genes to cells
Gene targeting
moves a gene to a particular location
Can genes be patented?
- not patentable (since 2013)
- transgenic organisms can be patented (must be new, useful and not obvious to an expert in the field)
- DNA patenting is controversial
BRCA1 and BRCA2
- patented by Myriad Genetics and University of Utah
- patients were forced to take Myriad's test which was expensive
- Patents discourages research and prevented second optinion
Polio
- mice don't get polio
- lack receptor for virus
- transgenic mice express human gene for polio receptor
- can be infected by polio virus
- develop characteristics of disease
transgenic sheep
- produce human protein alpha1-antitrypsin
-treat deficiency which causes damage to lungs/liver
GMO primates
- 2001 - 1st GMO monkey
- useless "marker" gene was inserted
- shows promise for human gene therapy
GMO primates 2009
- transplanted gene is heritable
- researchers now plan to create families of monkeys that develop neurodegenerative diseases similar to those seen in humans
Genetically modified primates and autism
- 2016: monkeys genetically modified to show symptoms of autism
- used CRISPR/Cas9 technology
- controversial case
Genetic technologies are possible because
genetic code is universal
Polymerase chain reaction (PCR)
- amplifying (copying) pieces of DNA to create many copies
- PCR uses: forensics, medical tests, genetic testing
DNA tool box
restriction enzymes cut DNA at specific locations (function like scissors)
DNA ligase
attaches 2 pieces of DNA together (glue)
Vectors
carry DNA to a new location
- plasmids
- bacteriophages
- retroviruses
Recombinant DNA technology
- human insulin
- 1st product produced through recombinant DNA technology
Transgenic organisms
- new traits introduced to organism
- requires moving DNA into cell
- plants: gene guns, Ti plasmid, and viruses
- Animals: chemicals that open membrane, liposomes, electricity, and injections
CRISPR - a game changer
- clustered regularly-interspaced short palindromic repeats
- short sequences of bacterial DNA that function as bacterial immune system
- can be used to cut eukaryotic genomes at very precise locations
- makes germline editing of human embryos possible
Current examples
- genome editing
- reversible knockout modification - creates epigenetic change by methylating gene
- activate genes
- create better disease models
- "gene drive" has been used to create mosquitoes that cannot carry malaria or are infertile
Release of genetically modified organisms
- microcosm experiments and field tests
- bioremediation: use of an organism's engineered abilities to remove toxins from the environment
Role of genetic counselors
- health care professionals trained in genetics and psychology
- educate public about genetic information
- evaluate risk based on personal and family history
- determine whether and which genetic tests are appropriate
- counsel patients before and after genetic test results
- act as a resource for referral or support group information
slide 3 ch. 20 types of genetic screening tests
see slide
Genetic counseling issues
- privacy (confidentiality within society and within family)
- nondirective information
- insurance
- role within the health care profession
Preconception comprehensive carrier testing
- a single test that detects recessive mutations of 448 diseases
- severe phenotype
- several mutations known
- penetrance is high
Nutrigenetics testing
- direct to consumer DNA test coupled with questionnaire about lifestyle, diet, etc.
- government accountability office study: don't waste your money!
Pharmacogenetics
- using genetics to match patients to drugs and doses
- identifying patients likely to suffer a negative reaction to a drug
- select the most effective drug/dose
- monitor response to drug treatment
- predict course of the illness
Gene therapy
replaces malfunctioning gene - alleviate symptoms
- controversial science (successes and failures)
Eugenics
- effort to breed better humans - encouraging reproduction of people with "good" genes and discouraging those with "bad" genes
Somatic
alters somatic cells - not passed to next generation
Germline
alters germ cells - passed to next generation (not done in humans)
Therapeutic
attempt to cure a disease
Enhancement
attempt to choose a child's traits (strength, heigh, intelligence)
Ex vivo
genetic alteration of cells removed from patient and implanted back into patient
In vivo
direct genetic manipulation of cells in the body - more invasive
Early success: Severe combined immunodeficiency (SCID)
- disease in which immune system is nonfunctional (lack of T and/or B cells)
- ADA deficiency
- X-linked SCID
- only human disease to be cured by gene therapy
First gene therapy patient - ADA deficiency
- Ashanthi DeSilva
- gene therapy in 1990 at age 4
- she is now 26 and doing well
X-linked SCIDS - successes and failures
- 14 children treated with gene therapy
- 3 developed leukemia (one died)
- insertion of retroviral vector near proto-oncogene LMO2 promoter led to uncontrolled proliferation of mature T cells
- 11 others are cured
Serious setback: OTC trial
- ornithine transcarbamylase deficiency
- lack of enzyme that helps break up proteins
- ammonia accumulates in blood
- Jesse Gelsinger: volunteered for gene therapy at age 18, died 4 days later due to a massive immune response
More recent success
- gene therapy for Leber congenital amaurosis type 2 (LCA2) - inherited form of blindness
- gene therapy trials on sheep dogs gad successfully treated the disease
- Corey Hass (age 8) received gene therapy in 2008
- Adeno-associated virus (AAV) carried wild-type version of gene into Corey's eye, he can see
Infertility
inability to conceive after 1 yr w/o contraceptives
- 1/6 couples: trouble conceiving in US
- 90% physical basis
- 30% male infertility
- 60% female infertility
- 20% both
Male infertility (Oligospermia) (1/30 men)
- normal sperm count: 20-200 million/mL
- count < 20 million/mL = oligospermia
- can have a genetic cause (Y chomosome)
- reproductive technologies can cause infertility to be passed on to offspring
Antisperm antibodies
- blood-testes barrier prevents antibodies from getting to sperm
- if barrier is broken, immune response can result
Too much heat
- ex. varicose vein in scrotum causes too much heat near developing sperm and they can not mature
(too tight underwear, laptop in lap, hot tubs)
Genetic causes
lack of gene of Y chromosome that controls spermatogenesis
- mutation in gene for androgen receptor (androgen-regulated genes required for spermatogenesis and sexual differentiation)
- testicular feminization
- infertility
Decreased sperm motility
- physical defects
Female infertility
- hormonal problems
- irregular menstruation
- polycystic ovarian syndrome (increased androgen levels lead to cysts), early menopause
- pelvic inflammatory disease (bacteria infect reproductive organs) - leading cause of female infertility w 100,000 women/yr
- endometriosis - tissue builds up in uterus and outside of uterus causing scarring and inflammation
Ectopic pregnancies
- fertilized ovum implants on tissue other than endometrial lining of uterus
- 40/50 women die/ year in US
Infections
STDs and other infections can damage reproductive organs
Surgical problems
- scar tissue does not allow implantation
Infertility tests: Laparoscopy
x
Assisted reproductive technologies
- replace source of male/female gamete, aid fertilization or pregnancy
- surrogate pregnancy
- in vitro fertilization
- sperm or egg donor
- worldwide - about 250,000 births a year
Intrauterine Insemination (donated sperm)
- donated sperm placed in woman's reproductive tract (success is 5-15% per try)
- 1790: 1st reported pregnancy from IUI
- 1953: methods for freezing/storing sperm
Sperm banks
- cost: ~$125-$615 (cost difference due to education level and more complete medical history information)
- couples can choose sperm from catalogues that lists features of donors (including non-genetic traits)
Surrogat motherhood
- woman carries pregnancy to term for woman who cannot conceive and/or carry pregnancy
In vitro fertilization (IVF)
- sperm fertilizes egg in culture dish
- embryos transferred to uterus for implantation
- 1978 first IVF child
- ~25% success rate
- higher rate of birth defects than natural birth
Intracytoplasmic sperm injection (ICSI)
- IVF accompanied by injection of sperm into oocyte
- used in cases of low sperm count, abnormal sperm shape, sperm motility problems
Gamete/zygote intrafallopian transfer
- gamete/zygote placed in woman's uterine tube
- done less often than IVF
- can't be done if woman has excessive scarring
Oocyte donation
- eggs stored frozen (in metaphase II until fertilization occurs)
- women can store own eggs (have children later, undergoing chemotherapy, work with teratogens)
- donated eggs can be used by women with infertility problems
- embryo adoption
- cytoplasmic donation (older women have oocytes injected with cytoplasm from oocytes of younger women)
- recipients of donated oocytes, embryos, and cytoplasm can be up to 55 years of age
Preimplantation genetic screening and diagnosis (PGD)
- detection of genetic abnormalities
- 1 cell of 8-celled embryo removed, remaining cells complete development
- 1992: 1st child born following pGD to screen for CF allele
- combined w/ IVF for women with multiple miscarriages
Extra embryos
- there are approximately half a million extra embryos derived from IVF being stored in US
- fates: store, donate for research, done to another couple, discard
Embryonic stem cells
- IVF produces extra embryos
- embryos made up of embryonic stem cells (pluripotent cells)
- research indicates therapeutic uses: Parkinson's, Alzheimer's, diabetes, spinal cord injuries
- parents can donate these cells to science
- fetal stem cell technologies are controversial (destruction of embryos, ethically questionable research)
Polar body biopsy
- polar bodies can be analyzed for genetic problems
- only health oocytes used for IVF - should increase success of IVF and decrease number of excess embryos
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