GENE - Principles of Genetic Inheritance

Question 1

Describe autosomal dominant pedigrees

Answer 1

• affected offspring have one affected parent
• unaffected individuals do not transmit trait (no silent carriers)
• trait expected in every generation at 50%

Question 2

Describe autosomal recessive pedigrees

Answer 2

• 2 copies of mutant allele is required
• if one copy is present, individual is only a carrier
• if two carriers procreate, 25% offspring will be unaffected, 25% will be affected and 50% will be an unaffected carrier

Question 3

Describe X-linked recessive pedigrees

Answer 3

• females rarely affected; primarily heterozygous carriers
• unaffected males don’t transmit trait
• males express phenotype with 1 allele, whereas females need 2 alleles present
• no father-son transmission, as males receive Y chromosome from father
• if mother expresses recessive phenotype, all of her sons will be affected

Question 4

What is lyonization?

Answer 4

• When an additional X chromosome is inactivated (not transcribed)
• Pattern of inactivation is random and occurs separately in individual cells during development

Question 5

Describe mitochondrial inheritance pedigrees

Answer 5

• mitochondria are inherited only through mother
• affected females transmit to all offspring
• affected males transmit to NONE of their offspring

Question 6

What is the mitochondrial threshold effect?

Answer 6

The severity of mitochondrial mutation correlates to the presentation of the disease. There is a threshold number that must be crossed in order for disease to present.

Question 7

What does LHON stand for?

Answer 7

Leber hereditary optic neuropathy

Question 8

What occurs in the mitochondrial disorder, LHON?

Answer 8

Degeneration of retinal ganglion cells, leading to a dark circle in field of vision

Question 9

What does MERRF stand for?

Answer 9

Myoclonic epilepsy and ragged red fibers

Question 10

What occurs in a MERRF mitochondrial defect?

Answer 10

• mutation in gene encoding for tRNA of lysine

- disrupts synthesis of cyctochome-c oxidase

Question 11

What are the signs and symptoms of MERRF?

Answer 11

Myoclonus dinated muscle movement, cerebral ataxia, seizures, myopathy, and dementia

Question 12

What does MELAS stand for?

Answer 12

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Question 13

What happens when a MELAS mitochondrial disorder is present?

Answer 13

• most common mitochondrial inherited disease
• affect many systems, including brain, nervous system, and muscles
• may cause stroke and dementia, diabetes, deafness, cognitive impairment, short stature, and migraines

Question 14

What does euploid mean?

Answer 14

Cells have a normal number of chromosomes

Haploid gametes and diploid somatic cells

Question 15

What does nondisjunction mean?

Answer 15

• Abnormal separation of homologous chromosomes or sister chromatid
• occurs at anaphase of mitosis, meiosis I or meiosis II

Question 16

What is polyploidy?

Answer 16

• Cells contain a complete set of extra chromosomes in a cell
• Incompatible with human life, often seen in plants

Question 17

What is aneuploidy?

Answer 17

• Cells contain a missing or additional individual chromosome
• Monosomy and trisomy

Question 18

What is the karyotype of Turner Syndrome?

Answer 18

45, XO

Question 19

What are some of the signs and symptoms of Turner Syndrome?

Answer 19

Short stature, ovarian hypofunction, premature ovarian failure, infertility, webbed neck, extra skin, low hairline, lymphedema, and cardiovascular defects
Possible developmental delays

Question 20

What is the karyotype of Klinefelter Syndrome?

Answer 20

47, XXY

Question 21

What are the signs and symptoms of Klinefelter Syndrome?

Answer 21

• Varying degrees of cognitive, social, behavioral, and learning difficulties
• Primary hypogonadism (low testosterone), small and/or undescended testes
• Gynecomastia, infertility, less dense body hair
• Variability in X numbers can increase symptoms (48, XXXY; 49 XXXXY)

Question 22

What is another name for Trisomy 21?

Answer 22

Down Syndrome

Question 23

Which chromosomes affected by trisomy are compatible with life? Which are not?

Answer 23

Trisomy 13, 18, and 21 are compatible with life. The rest are not

Question 24

What are some of the signs and symptoms of Trisomy 21?

Answer 24

Short stature, distinct facial features, cardiac defects, duodenal atresia, ventriculomegaly, absent nasal bone, and short limbs

Varying degrees of cognitive impairment

Question 25

What is another name for Trisomy 18?

Answer 25

Edwards Syndrome (47, XX/XY,+18)

Question 26

What are the signs and symptoms of Trisomy 18?

Answer 26

Microencephaly, prominent occiput, malformed and low-set ears, small mouth and jaw, cleft lip/palate, rocker bottom feet, and overlapping fingers. Rocker bottom feet is a tell-tale sign of trisomy 18 Approximately 95% of fetuses die in utero, and less than 10% of those born alive survive to 1 year of age.

Question 27

What is another name for Trisomy 13?

Answer 27

Patau Syndrome

Question 28

What are the signs and symptoms of Trisomy 13?

Answer 28

Severe intellectual disabilities and physical abnormalities, heart abnormalities, kidney malformation, CNS malformation, microcephaly, malformed ears, closely spaced/absent eyes, clenched hands and plydactyly, and cleft lip/palate

Question 29

Define genomic imprinting

Answer 29

Alleles that are silenced (not transcribed) such that the gene is expressed only from the non-imprinted allele of the mother or father

Question 30

What is uni-parental disomy?

Answer 30

When an individual receives two copies of a chromosome from one parent and no copies from the other parent Occurs as a random error during meiosis Can lead to Prader-Willi and Angelman Syndromes

Question 31

What are the symptoms of Pradder-Willi Syndrome?

Answer 31

Short stature, hypotonia, small hands/feet, obesity, intellectual disability, uncontrolled eating, and behavioral complications

Question 32

What are the symptoms of Angelman Syndrome?

Answer 32

Severe intellectual disability, speech impairment, seizures, ataxic gait, and excitability

Question 33

What causes Prader-Willi Syndrome?

Answer 33

Spontaneous deletion/mutation of PATERNAL chromosome 15

Question 34

What causes Angelman Syndrome?

Answer 34

Caused by a deletion/mutation in MATERNAL chromosome 15

Question 35

Define penetrance in relation to genetics

Answer 35

The probability of expressing a particular phenotype If < 1.0, genotype is said to have incomplete penetrance

Question 36

Define variable expressivity

Answer 36

Trait in which the same genotype can produce phenotypes of varying severity or expression

Question 37

Variable expressivity depends on many environmental factors. Name a few.

Answer 37

Diet, exercise, exposure to harmful agents, etc.

Question 38

What are two examples of Variable Expressivity diseases mentioned in lecture?

Answer 38

Neurofibromatosis - Mild expression: cafe-au-lait spots, benign growths on iris, nerve tumors - Severe expression: thousands of nerve tumors, optic nerve gliomas, learning disabilities, hypertension, scoliosis, and malignancies Marfan Syndrome - Affects connective tissue, subsequently affecting many different systems - Ectopia lentis and weakened and stretched aorta - May lead to aneurysm and aortic dissection

Question 39

What is locus heterogeneity?

Answer 39

Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci Example: osteogenesis imperfecta (chromosome 7 and 17)

Question 40

Define genotype frequency

Answer 40

Number of individuals with a given genotype divided by the total number of individuals in the population Three possible genotypes: homozygous dominant, homozygous recessive, and heterozygous Frequencies are denoted as p2, q2, and 2pq

Question 41

Define allele frequency

Answer 41

Frequency of occurrence or proportions of different alleles of a particular gene in a given population Two possible alleles: Dominant and Recessive Frequencies denoted as p and q

Question 42

What does the Hardy-Weinberg Principle state?

Answer 42

Specifies the relationship between allele frequency and genotype frequency p^2 + 2pq + q^2 = 1 ``` p = dominant allele frequency, q = recessive allele frequency p^2 = homozygous dominant genotype frequency q^2 = homozygous recessive genotype frequency 2pq = heterozygous genotype frequency ```