Genetics Exam 2

contains either more or less of the number of chromosomes than the normal diploid number for the species -sometimes is compatible with life, sometimes is not

having one set of chromosomes (23 in humans) -not compatible with life

inheritance of an extra copy of one chromosome -trisomy 21 is compatible with life but others are not -either stillborn or die by 1

when additional whole sets of extra chromosomes are present (triploidy, 69 chromosomes, 3N) -not compatible with life

normal diploid number of chromosomes for the species -compatible with life

Chromosomal abnormality in which all or part of a chromosome is transferred to another nonhomologous chromosome

The right amount of DNA is present but not all the DNA is located in its customary place, no specific risk exists for abnormal development or miscarriage as a fetus

Reciprocal- where segments of 2 non-homologous chromosomes break and are equally exchanged, development and phenotype aren't affected Robertsonian- created by the fusion of the entire q arms of 2 acrocentric chromosomes with the loss of the p arms

2 or more different karyotypes are consistently present in 1 individual, some cells have an abnormal karyotype and others are normal -can be tissue specific, but not evenly distributed -mutation occurs after fertilization in embryonic period -may explain the variance in chromosomal disorders -how it affects a person depends on the tissue involved For example, A person could have 30% cells with trisomy 21 and 70% without and the person is not affected. This could be because none of the cells with trisomy 21 are located in the brain

Extra X- X inactivation Extra Y- there is not a lot of genes on it

45X -most common chromosome issue conceived but most are lost as early miscarriage -live born infants are thought to have undiagnosed mosaicism -short stature and decreased growth rate -pedal edema in newborns -neck webbing -kyphosis, scoliosis -osteoporosis -hypertension -cardiac issues

47 XXY -caused by maternal or paternal nondisjunction -normal infant and childhood male phenotype -greater than average height with long legs -low testosterone levels and high FSH levels -small testes and penis -slightly lower IQ -gynecomastia -decreased libido -infertility -at risk for leukemia -less than average or no sperm production -various health problems

Silencing of FXMR1 gene (brain development and neuron maintenance) -degree of expression is related to number of repeat sequences -features become more apparent with age -expression is less severe in women -ASD -poor balance -long narrow face -large ears -prominent jaw -high anxiety -reduced cognition -gets worse from generation to generation

Trisomy 21 -decreased intellectual development -congenital heart defects -palmar/simian crease on palms -flat faces -widely spaced eyes -low-set ears

Prader-Willi Syndrome -deletion of paternal chromosome 15 from q11-q13 -only maternal expression of alleles -features are normal at birth -infant problems: hypotonia, poor sucking reflex, failure to thrive, developmental delays, insatiable appetite, and short

Angelman Syndrome -deletion of maternal chromosome 15 from q11-q13 -only paternal expression of alleles in this region -features are normal at birth -overtime significant cognitive and physical problems develop -speech greatly impaired

Mutations in the mtDNA (only codes for about 37 genes) -neuromuscular -skeletal ???

Circle=woman Square=man Triangle=unknown sex Horizontal line=mating, male on left, woman on right Vertical lines=lines of descent Horizontal slash=deceased Arrow=proband

1. Who expresses the disorder male or females or both?

2. Who passes on the disorder males or females or both?

3. Who inherits the disorder males or females or both?

4. Do you see the disorder in every generation, does it show up in a lot of people, does it show up in siblings?

Autosomal recessive disease that affects a person's iron absorption -white people are at a higher risk -can be environmentally impacted by diet, menstruation, and other factors -related to the excessive absorption of iron throughout life, iron becomes deposited in many of the body's organs -iron deposits in the pituitary gland can affected the control of one's sex hormones leading to amenorrhea and impotence Tests -screening tests -genetic analysis

Important to inform diagnosis promote risk assessment family history can help in risk factors for CAD benefit of targeted pedigree for CAD -identify pattern of inheritance -typical age of onset -establish whether patient is at risk for something -collect data and make sure it is accurate

FGENES

Family history Group of congenital anomalies Extreme or exceptional presentation of common conditions Neurodevelopmental delay or degeneration Extreme or exceptional pathology Surprising lab values

Rule of two/too too short/tall too early too many too young too different two tumors two generations two in the family two birth defects

-three generations -full and half relationships -unaffected vs affected -who provided information -date of collection and name of collector -key -age, DOB, relevant health info, diagnosis, age of diagnosis, infertility or no kids, consanguinity, pregnancy and any complications

person in a family who brought the potential genetic issue to the attention of a health-care professional

person looking for information

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Diagnostic test- confirms a disorder or the presence of a specific mutation Screening test- calculates the risk of having a disorder or mutation

Analysis of DNA, RNA, chromosomes, proteins, and protein metabolites to identify heritable variations in genes and/or chromosomes -can be done for more than 5000 disorders -getting positive results can mean different things depending on the purpose of the test and the relationship of the mutation to the disorder

entail lab evaluation of gene products such as enzymes, hormones, or metabolites -when the gene product's quantity or quality is off it can be concluded that there is a problem with the gene -ex. newborn screening

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A single stranded sequence of DNA or RNA used to search for its complementary sequence in a sample genome -it is used in FISH too look for where certain mRNAs are expressed in a cell or in a tissue -used to screen the genome to find out if there are extra copies of certain parts of the genome

Known deletions put on a "slide" Take patient's DNA and make it single stranded If it binds then they know where the micro deletion is -alternate to karyotype analysis -can identify submicroscopic deletions and duplications -can identify SNPs -can identify genetic variations that we have very little info about -1st tier test for children with neurodevelopmental concerns

Analysis of the bases in a stretch of DNA -sequence of nucleotides in the exons, the intron/exon boundaries, or splice sites -possible sites of regulatory genes -most specific but most time consuming and expensive

a lab technique for detecting and locating a specific DNA sequence on a chromosome. The technique relies on exposing chromosomes to a small DNA sequence called a probe that has a fluorescent molecule attached to -can be done faster

Ability to accurately and reliably measure the gene/genotype -How well the test measures what it is supposed to measure -Sensitivity= How well a test identifies someone with the disorder -Specificity=How well a test identifies someone without the disorder

Ability to accurately and reliably identify disorder -How well the test predicts the development of the disorder/disease -genotype-phenotype relationship -penetrance -expressivity -measuring correct mutation for correct population

What are the risks and benefits of using this test in routine clinical practice -Will the test help in management of the disorder/disease -natural history of the disorder -effectiveness of interventions -adverse outcome of having the test done -available resources

-Different ethnic groups -screening vs diagnostic (initial test) -looking at family history -biochemical measures may be important, if disorder has low penetrance

-Results: positive, negative, unknown, margin of error -Screening or Diagnostic -Further testing -What will the results mean for the particular individual involved (penetrance, expressivity) -Limitation of Test (what it does and does not identify) -Mosaicism

-The disease must be serious, common, and treatable in some form -The test has to be accurate and reliable -The screening program needs to be available to all individuals who could benefit from it -Clear criteria for normal (-) and abnormal (+) results -Must be a clear understanding of what the test actually does measure

-know basic terms -understand basic patterns of inheritance -understand genetic tests commonly used in your practice area -assess your patient's family's understanding of genetic concerns ???

-may not test all coding sequences in the gene -inappropriate testing -misinterpretation of results -inaccurate tests -clinically invalid tests -lack of follow-up care -scientific evidence for the test -protection of consumer privacy

large abnormalities translocations trisomy, monosomy, etc. not very specific

-substantial public health burden -Clearly Defined Case Definition (suspected case vs known case) -awareness of disease among relatives -accurately reported by family members -family history is an established risk factor -effective interventions for primary and secondary prevention

Recommended Diseases- CAD, Type II diabetes, asthma, colorectal cancer, breast and ovarian cancer, and osteoporosis

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Assessment

1. Monitor health status to identify and solve community health problems

2. Diagnose and investigate health problems and health hazards in the community Policy Development

3. Inform, educate, and empower people about health issues

4. Mobilize community partnerships and action to identify and solve health problems

5. Develop policies and plans that support individual and community health efforts

6. Enforce laws and regulations that protect health and ensure safety Assurance

7. Link people to needed personal health services and assure the provision of health care when otherwise unavailable

8. Assure competent public and personal health care workforce

9. Evaluate effectiveness, accessibility, and quality of personal and population-based health services Research

10. Research for new insights and innovative solutions to health problems

-the consultant tests positive for one of the disorders -the first degree relatives are then tested for the specific mutation found in the consultant -then they test the first degree relatives of these relatives that tested positive and so on Common disorders tested for -Lynch Syndrome -Heritable Ovarian and Breast Cancer -Familial Hypercholesterolemia

How knowledgeable about genetic testing are many HCPs? -a majority have deficiencies in their understanding of genetics risk assessment and testing -a non-genetic provider may have neither the knowledge nor time to conduct comprehensive genetic counseling, including interpretation of results and making recommendations for cascade genetic screening

Is testing always covered by insurance? -Not always covered by insurance -varies from state to state and by health plan -low rate of reimbursement for comprehensive genetic counseling services

How does geographical location play a role? -There is a shortage of genetic specialists throughout the US especially in rural areas -People who live near big cities are more likely to be referred to a genetic specialist

How can cascade screening reduce testing costs? -More cost-effective than population screening as the risk of being a carrier is considerably higher among close blood relatives -identifies the most appropriate individual to test first -only requires single-site testing for the specific gene mutation, rather than testing for an entire gene

How can it reduce health care costs? -the cost of evidence-based cascade genetic screening strategies are lower than additional costs for disease management

How can it lead to more accurate diagnosis? -only requires single-site testing for the specific gene mutation, rather than testing for an entire gene

How can it improve outcomes? -improve population health outcomes by increasing early awareness among individuals who share the same hereditary condition -Identifying asymptomatic carriers in a family provides opportunities to asses hereditary risk, prevent disease by risk reduction, diagnosis disease in early stages, and improved clinical outcomes

Pros -very sensitive -identify things early on Cons -high rate of false positives -may cause parents to worry unnecessarily -small amount of blood for many disorders so might not be the msot accurate -may need further testing

-independent assortment of alleles -crossing over of segments of homologous chromosomes ???

Allele frequencies remain stable because of these criteria -no one migrates -people mate randomly -population is extremely large -everyone has children -there are no mutations

Beneficence- the obligation of a care provider to intend the maximal benefit of an offered intervention Non-maleficence- the obligation of a care provider to weigh the possible benefit of an offered intervention against any risk of harm and offer only those possible interventions that have a favorable risk to benefit ratio Respect for Autonomy- the belief that all clients, irrespective of background origin or current political status deserve to have their voices heard about decisions about their care Justice- the belief that fairness should be a part of health care resource decisions. Health providers should consider what patients deserve as part of their care and strive to provide that amount of resources

Information about person and their family

-The patient's diagnosis, if known; -The nature and purpose of a proposed treatment or procedure; -The risks and benefits of a proposed treatment or procedure; -Alternatives (regardless of their cost or the extent to which the treatment options are covered by health insurance); -The risks and benefits of the alternative treatment or procedure; and -The risks and benefits of not receiving or undergoing a treatment or procedure.

Genetic Information Nondiscrimination Act (GINA) -prevents employers or health insurers from discriminating against people due to their genetic information -does not prevent life insurers, disability, long-term care, or military members from using this information

-Identification of the genetic condition must provide a clear benefit to the child -A system must be in place to confirm the diagnosis -Treatment and follow-up must be available for affected child. -The AAP does not support the broad use of carrier testing or screening in children or adolescents.

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-African American women are more likely to get an inclusive test result when genetic testing is done for HBOC -African American men are more likely to get prostate cancer- but we don’t know why -Many ethnic groups native to the America’s are more likely to get T2DM ???

done to confirm or rule out a particular diagnosis in a symptomatic person

for asymptomatic people who want information about their risk of developing a genetic disease in the future -testing to see if they care a mutation for a disease that they will develop later on in life -ex. early onset alzheimers

done when persons have family members affected by a heritable disease, but they themselves are not affected -can be done for persons who are high at risk for genetic disease based on their ethnicity

can be done to determine if the fetus carries a specific gene variant or a chromosomal disorder

done to identify those infants at high risk of a variety of disorder for which immediate treatment or intervention is available