Content Outline

Below is the content outline of items available for the general and all primary specialty examinations. The general examination may contain some items from all sections of the outline. However, the items will be chosen to be at the knowledge level expected for non-specialist geneticists. Each specialty will contain items from the sections that are appropriate for that specialty and may include items that cross specialty knowledge areas. For example:

• Clinical and Medical Biochemical Genetics:

  • 01, 02 as appropriate, 03.C, 04., 05, 06

• Clinical Genetics

  • 01, 02 as appropriate, 04,05,

• Clinical Cytogenetics

  • 01,02 as appropriate,03.B, 06

• Clinical Molecular Genetics

  • 01, 02. as appropriate, 03.A, 06

01. Normal structure and function

1. Genes

   1. RNA and DNA structure (includes polymorphisms)

   2. Transcription/translation/regulation

      1. RNA processing

      2. Posttranslational processing

      3. Transcription

   3. Gene mapping/linkage

   4. Nomenclature

2. Chromosomes

   1. Chromosome structure

      1. Centromere

      2. Telomere

      3. DNA structures (Sines, Lines, ALU, etc.)

   2. Mitosis, meiosis, cell cycle

      1. Mitosis

      2. Meiosis

         1. Spermatogenesis

         2. Oogenesis

      3. Cell cycle regulation

   3. Chromosome/gene function

   4. Gene mapping/ somatic cell hybridization and in situ hybridization

3. Cells & Organs

   1. Metabolic pathways

   2. Cell biology

      1. Division

      2. Differentiation

      3. Migration

      4. Cell-cell interaction

      5. Cell-environment interaction

      6. Apoptosis

4. Humans

   1. Embryology

   2. Development

   3. Pedigrees

   4. Expressivity, penetrance, pleiotropy, heterogeneity, etc.

5. Populations

   1. Hardy-Weinberg

   2. Mutation selection

   3. Haplotype analysis

   4. Inbreeding

   5. Evaluation

02. Classification of Abnormalities/Pathogenesis

1. Genes

   1. Types of mutations

      1. Germline

         1. Triplet expansion disorders

         2. Single nucleotide disorders

         3. Rearrangements (including deletions, insertions, inversions, duplications)

         4. Polymorphisms

      2. Somatic

         1. Point mutations

         2. Loss of heterozygosity (LOH)

   2. Nomenclature

   3. Pathogenesis/Etiology

   4. Other

2. Chromosomes

   1. Types of chromosome abnormalities

      1. Constitutional chromosome syndromes

         1. Autosomal

            1. Polyploidy

            2. Aneuploidy

            3. Structural rearrangements

               1. Deletions, microdeletions

               2. Duplications

               3. Inversions

               4. Insertions

               5. Translocations

               6. Isochromosomes

               7. Rings

               8. Markers

               9. Other

         2. Sex chromosomal

            1. Aneuploidy

            2. Structural rearrangements

         3. Chromosome breakage

         4. Uniparental disomy

         5. Sister chromatid exchange

         6. Mosaicism

         7. Chimerism

      2. Acquired chromosome disorders (cancer)

         1. Hematologic malignancies

            1. ALL

            2. AML

            3. CML

            4. CLL

            5. Myelodysplasia

            6. Multiple myeloma

            7. Other

         2. Solid tumors

            1. Neuroblastoma

            2. Wilms tumor

            3. Lymphoma

            4. Synovial sarcoma

            5. Ewing’s sarcoma

            6. Other

   2. Nomenclature

      1. Constitutional

         1. Polyploidy

         2. Aneuploidy

         3. Structural rearrangements

            1. Deletions

            2. Duplications

            3. Microdeletions

            4. Isochromosomes

            5. Translocations

            6. Inversions

            7. Insertions

            8. Other

      2. Acquired

      3. FISH

   3. Pathogenesis

      1. Nondisjunction

      2. Unequal crossing over

      3. Abnormal segregation

      4. Mosaicism

      5. Other

3. Cells & Organs

   1. Biochemical disorders - abnormalities of cell metabolism

      1. Types of abnormalities

         1. Enzymopathies

         2. Receptor, transporter, structural protein (e.g., hemoglobin)

         3. Disorders of development (e.g., cholesterol metabolism disorders)

         4. Cell biological disorders (e.g., lysosome formation disorders)

         5. Mitochondrial disorders

         6. Contiguous gene syndromes

   2. Abnormalities of cell division

   3. Abnormalities of cell differentiation

   4. Abnormalities of cell migration

4. Human diseases

   1. Single gene disorders

      1. Metabolic

      2. Dysmorphology

         1. Malformation

         2. Dysplasia

      3. Nondysmorphic syndromes

         1. Blood

         2. Brain malformation

         3. Cancer

         4. Craniofacial

         5. Ear (+ hearing)

         6. Endocrine

         7. Eye

         8. Genital

         9. GI

         10. Hamartoma

         11. Heart

         12. Immune

         13. MCA

         14. Mental retardation

         15. Metabolic

         16. Neuromuscular

         17. Overgrowth

         18. Psychiatric

         19. Pulmonary

         20. Renal

         21. Skeletal

         22. Skin (includes hair, nails)

      4. Pedigree Patterns

   2. Chromosomal disorders

      1. Autosomal

      2. Sex chromosomal

   3. Multifactorial disorders

      1. Birth defects

         1. Cleft lip and palate

         2. CHD

         3. Pyloric stenosis

         4. CNS malformation

         5. Limb malformation

      2. Common/chronic complex diseases

         1. Cancer

         2. Psychiatric disorders

         3. Vascular disease/coronary artery disease/stroke/hypertension

         4. Mental retardation/autism

   4. Mitochondrial

      1. Maternal Inheritance

      2. Disorders

         1. Neurological

         2. Muscle

         3. Other (deafness, diabetes, etc)

   5. Environmental

      1. Teratogens

         1. Drugs

         2. Methylmercury, lead, solvents

         3. Infections

      2. Uterine constraint (deformations)

      3. Disruption

      4. Maternal disease

         1. Diabetes mellitus

         2. Androgen excess

         3. PKU

         4. Hyperthyroidism

      5. Pharmacogenetics

   6. Twinning (including placentation)

5. Populations

   1. Types of abnormalities

      1. Mating systems

         1. Consanguinity

         2. Assortive mating

         3. Admixture

         4. Linkage-association

         5. Meiotic drive

      2. Genetic isolates

   2. Pathogenesis

      1. Genetic drift

      2. Founder effect

      3. Inbreeding

   3. Gene Frequencies

      1. Hardy-Weinberg

      2. Other

03. Laboratory Techniques (to identify the things that can go wrong)/Applications (situations in which they would be used)/Interpretation Issues

1. Clinical molecular genetics

   1. Techniques

      1. Mutation analysis

         1. Basic principles

         2. Automation

      2. Mutation scanning

         1. Basic principles

         2. Automation

      3. Sequence analysis

         1. Basic principles

         2. Automation

      4. Linkage

      5. Polymorphism

         1. HLA analysis

         2. Identity

      6. Core procedures

         1. PCR

            1. RTPCR

            2. Real time

         2. DNA isolation

         3. Sequencing

         4. Gene transfer

   2. Applications

      1. Diagnosis of a symptomatic person

      2. Predictive testing

         1. Hereditary disease (presymptomatic)

         2. Pharmacogenetic/ecogenetics

      3. Prenatal diagnosis

      4. Preimplantation diagnosis

      5. Carrier testing

      6. Screening

         1. Population-based

         2. Preconceptual

      7. Identity testing

         1. Paternity

         2. Forensic

         3. Kindred reconstruction

   3. Test interpretation issues

      1. Genotype:phenotype correlations

      2. Residual risk calculation

      3. Ethical/legal

      4. Test limitations

      5. Recommendations

2. Clinical cytogenetics

   1. Techniques

      1. Cell culture

         1. Blood

         2. Skin

         3. Amniocytes

         4. CVS

         5. Bone marrow

         6. Solid tumor

         7. Lymphoblasts

      2. Chromosome preparation

      3. Banding techniques

      4. Microscopy/Karyotyping

      5. FISH/CGH/Microarrays

      6. Specialized cytogenetic studies (eg, breakage, SCE)

   2. Applications

      1. Diagnosis of a symptomatic person

      2. Cancer

         1. Diagnostic

         2. Prognostic

      3. Prenatal

         1. Abnormal pregnancy

         2. Screening (eg, AMA, abnormal maternal screen)

      4. Carrier (inherited rearrangement)

   3. Test interpretation issues

      1. Genotype:phenotype correlations

      2. Residual risk calculation

      3. Ethical/legal

      4. Test limitations

      5. Recommendations

3. Clinical biochemical genetics

   1. Techniques

      1. Enzyme assay

      2. Analyte assay

         1. Organic acids

         2. Amino acid analysis

         3. Other

   2. Applications

      1. Diagnosis of a symptomatic person

      2. Carrier

      3. Population-based

         1. Newborn screening

         2. Other

      4. Prenatal

   3. Test interpretation issues

      1. Genotype:phenotype correlations

      2. Residual risk calculation

      3. Ethical/legal

      4. Test limitations

      5. Recommendations

04. Clinical Techniques (to identify the things that can go wrong)

1. Genetic disease recognition

   1. Prenatal

   2. Pediatric

   3. Adult

   4. Measurements/physical activity

   5. Phenotype delineation/definition - in genetic research

2. Risk assessment

   1. Pedigree analysis/mode of inheritance

   2. Penetrance/expressivity

   3. Probability/recurrence risk

   4. Probability/Bayes theorem

3. Population screening

   1. Newborn screening

   2. Ecogenetics/workplace exposures

   3. Other

4. Genetic testing of individuals

   1. Genotype: phenotype correlations

   2. Symptomatic/diagnostic

   3. Presymptomatic/predictive (heterozygote potentially affected)

   4. Carrier testing (heterozygote unaffected)

   5. Prenatal/preimplantation

05. Clinical Management of an individual

1. Prevention of primary manifestations

   1. Diet

   2. Drugs/pharmacogenetics

   3. Lifestyle/behavioral

   4. Prophylactic surgery

   5. Gene therapy

2. Surveillance for complications/early detection of complications

3. Avoidance of environmental triggers

4. Symptomatic treatment

   1. Diet

   2. Drugs/pharmacogenetics

   3. Enzyme replacement therapy

   4. Bone marrow transplantation

   5. Organ transplantation

   6. Gene therapy

5. Counseling

   1. Legal/ethical issues

   2. Psychosocial issues

   3. Reproductive

   4. Anticipatory guidance

06. Laboratory management

1. Record keeping

2. Quality assurance/quality control

   1. Proper sample preparation procedures

   2. Avoidance of contamination

   3. Proper labeling

3. Automation

4. Ethical/Legal

5. Laboratory safety

6. Other