Exam 1 Genetics Thread Flashcards

Question

Spermiogenesis

Answer 1

Radical morphological change of spermatids into mature spermatozoa. * Acrosome creation * Shedding of cytoplasm * Middle piece formation ⇒ lost of mitochondria * Flagellum development

Answer 2

1º oocyte (arrested in prophase I) housed in layer of flat epithelial cells. Begin to mature into primary follicles at puberty.

Answer 3

**Primordial follicle ⇒ 1º follicle ⇒ 2º follicle ⇒ 3º follicle ⇒ graafian follicle.** **Primary oocyte** completes _meiosis I_ three hours prior to ovulation producing a **secondary oocyte** (haploid, 2N DNA) + first polar body. _FSH_ surge triggers **ovulation**. Secondary oocyte only completes meiosis II if fertilized by sperm.

Answer 4

* Epithelial cells of **primordial follicle** become cuboidal ⇒ now considered a **primary follicle** * **FSH** stimulates 1º follicle to form more cuboidal cells * Cells now called **granulosa cells** * Provides nutritional and hormone support

Answer 5

**1º follicle** ⇒ **2º follicle** when: * Z**ona pellucida** forms around 1º oocyte * Mucopolysaccharide layer * **Liquor folliculi** accumulates Primary oocyte and surrounding granulosa cells remain on one side of the follicle.

Answer 6

* Sits on cushion of granulosa cells called **cumulus oophorous**. * Provides nourishment and support * **Liquor folliculi** continues to accumulates * Becomes a **3º follicle** when the **follicular antrum** becomes large and filled with fluid

Answer 7

* Outer **thecal cells** divide into two layers: * **Theca interna** * procudes androgens that granulosa cells convert into estrogens * **Theca externa** * Vascularized * Provides nutritional support * Continues to enlarge * Usually only one 3º follicle will become a **graafian follicle**

Answer 8

3 hours prior to ovulation the **1º oocyte** within the **graafian follicle** will complete **meiosis I** to form a **2º oocyte**. FSH surge triggers follicle rupture and ovulation. Releases **2º oocyte, zona pellucida, and corona radiata.** Remaining granulosa cells become the **corpus luteum**.

Answer 9

Provides protection and nutrition to the developing spermatozoa.

Answer 10

Disease caused by pathogenic mutations in an individual allele or pair of alleles at a single genetic locus (1 gene).

Answer 11

Disease due to aberrations of one or more chromosomes. Two main groups: Those caused by abnormalities in the number of chromosomes. Those caused by abnormalities in chromosome structure.

Answer 12

Due to the interaction of multiple genes as well as environmental factors. Do not follow a Mendelian pattern of inheritance.

Answer 13

Results from mutations not present at the time of conception.

Answer 14

Single nucleotide polymorphism **A single base pair change anywhere in the genome.**

Answer 15

Simple sequence repeat polymorphisms. **Stretches of DNA with di-, tri-, or tetranucleotide repeat sequences.** The actual number of repeats varies in individuals.

Answer 16

Repeats of ten to hundreds of bases where the number of repeats varies between individuals.

Answer 17

Different numbers of copies of specific DNA sequences.

Answer 18

**A state where only a single allele exists at a given locus in an otherwise diploid cell.** Ex. normal males are hemizygous for all X chromosome alleles.

Answer 19

**Parental genes are randomly seperated during meiosis** so that each gamete contains only one gene of the pair.

Answer 20

Genes for different traits **independently seperate from one another during meiosis**, giving traits an equal opportunity of occuring together.

Answer 21

An organism with alternate forms of a gene wil express the form that is dominant.

Answer 22

* Assume that affected individuals are **heterozygous** unless there is other information * Both a **verticle and horizontal pattern of inheritance**. * **♂ and ♀ equal in frequency and severity** * Males can transmit disease * Offspring of affected individual with 50% chance of inheriting disease

Answer 23

* ♂ and ♀ equal in frequency and severity * Pedigree * **Rare trait ⇒ single sibship (horizontal pattern in 1 family)** * Common trait ⇒ scattered families with the trait * Risk of disease increases with **consanguinity**

Answer 24

An individual with 2 different mutated alleles at a given locus.

Answer 25

An individual who by pedigree analysis must carry a gene but otherwise has a normal phenotype.

Answer 26

Dosage compensation for two X-chromosomes in females through transcriptional silencing via non-coding RNA. 1. ***XIST*** (X-inactive specific transcript) gene expressed by the **X chromosome that is undergoing silencing**. 2. **ncRNA** produced coats the chromosome that made it. 3. Recruits silencing protein complexes. 4. Results in DNA methylation and histone hypoacetylation. 5. Condensation into a **Barr body** XIST only expressed in cells containing 2 or more X chromosomes. X inactivation is **random** except for **placental cells** which undergo **imprinted inactivation of the paternal X chromosome**. Results in **mosaicism** of cells in females.

Answer 27

* **No male to male transmission** * Affected males with normal sons and carrier daughters * Mother of sporadic affected male can: * Be heterozygous * Have mosaic gametes * Affected male + heterozygous female could look like autosomal dominant on pedigree * 1/2 ♂ affected ⇒ likes like ♂ to ♂ transmissions * 1/2 ♀ affected as severely as hemizygous ♂

Answer 28

* Females affected twice as often as males * Males often more severely affected than females * Affected females ⇒ 1/2 of ♂ and 1/2 of ♀ * If the disorder is lethal in utero in hemizygous males * only see affected females * affected females have fewer sons than daughters * affected females have more spontanous abortions

Answer 29

* Only males affected * Only male to male transmission

Answer 30

* *SRY* gene codes for sex-determining region Y protein * Transcription factor causes fetus to develop as a male * *SRY* mutations gives rise to XY females with gonadal dysgenesis * Translocation of SRY gene from Y to X chromosome results in 46,XX testicular disorder of sex development * Present in phenotypic females who lack functional androgen receptors

Answer 31

A trait that is only expressed in one sex. Ex. BRCA-1 and BRCA-2 mutations cause ovarian cancer in females only.

Answer 32

A trait that is expressed differently in the two sexes. Ex. BRCA-1 and BRCA-2 mutations cause different instances of breast cancer in females and males.

Answer 33

* **Maternally inherited** * No male to male transmission * Carrier will have both normal and defective mtDNA ⇒ **heteroplasmy** * Ratio of defective/normal mtDNA in ova will affect inheritance, severity, and onset ⇒ **threshold effect** * Mitochondrial donation ⇒ "three-parent" inheritance * Female pronuclei of a person with known mitochondrial disease inserted into cell with normal mitochondria

Answer 34

A mixture of two or more mitochondrial genotypes within a cell or individual. Ratio of normal vs altered mtDNA can influence the severity and timing of disease onset ⇒ **threshold effect**

Answer 35

**% of mutant mtDNA must be above a threshold to produce clinical manifestations.** * Threshold varies according to tissue oxidative need * Brain, heart, and muscle most * % of mutant mtDNA in daughter cells can shift during cell division ⇒ **mitotic segregation** * mtDNA can surpass pathogenic threshold in just one tissue ⇒ **skewed heteroplasmy**

Answer 36

Sudden appearance of an **autosomal dominant** or **X-linked recessive trait** assumed to be a **sporadic case** caused by a **new mutation.** Ex. 1/3 of new cases of Duchene muscular dystrophy (DMD) represent a new mutation. * De novo mutation in offspring ⇒ nearly zero chance of recurrence * De novo mutation in parent ⇒ recurrence risk varies and can approach 50%

Answer 37

Mutation occurs very early in pre-embryo or embryo before seperation of germline cells from somatic cells. Can be present in the germ and/or somatic cells. Can result in phenotypic expression and/or transmission to offspring.

Answer 38

Mutation effects somatic cells only. Will affect the tissue(s) that arise from those cells. Will have little effect onse the embryo has reached a certain size. Will not be transmitted to offspring.

Answer 39

Mutation in germ line cell precursor persists in all the clonal descendant of that cell. Individuals will have normal phenotype and normal DNA tests but likely to have multiple affected offspring. Strongly suspected when phenotypically normal parents have two or more offspring with autosomal dominant disease.

Answer 40

When a single gene influences multiple phenotypic traits including those that seem unrelated.

Answer 41

**The observable expression of a phenotype given presence of a genotype.** **All-or-none** in an _individual_. **Reduced penetrance** or **incomplete penetrance** used to describe a _population_.

Answer 42

The quantitative and qualitative phenotypic differences among individuals who carry the same mutation.

Answer 43

A **static mutation** could lead to a phenotype that could develop over a broad age range.

Answer 44

**Phenotype becomes more severe from one generation to the next.** * Indications of anticipation: * earlier age of onset with each generation * increasing severity with each generation * Usually due to **dynamic mutations** ⇒ expansion of trinucleotide repeats * **Threshold** number of repeats must be reached for disease manifestation

Answer 45

Different alleles of the same gene underlie disease. May lead to the same disease or a different disease.

Answer 46

Mutations in different loci leading to a clinically similar disease.

Answer 47

**The expression of one gene depends on the presence or absence of one or more nonallelic "modified" genes.** Means that most phenotypes are affected by more than one gene. * Whenever two or more loci interact to creat new phenotypes * Whenever an allele at one locus makes the effects of alleles at one or more other loci * Whenever an allele at one locus modifies the effects of alleles at one or more other loci

Answer 48

The study of heritable changes in gene expression that are not due to changes in DNA sequence. * Changes may be reversible or permanent * Usually due to DNA methylation * Can be influenced by environmental events * During embryogenesis widespread, almost complete demethylation occurs which must be re-established.

Answer 49

The differential expression of alleles depending on the parental source.

Answer 50

**Chromosomes 13, 14, 15, 21, 22, and Y** * Have masses called **satellites** attached to **short arm** by **stalks** (secondary constrictions) * Short arm contains hundreds of copies of **genes encoding ribosomal RNA** * Includes **nucleolus organizer regions (NORs)** critical for nucleolus formation

Answer 51

The numbered banding pattern of a chromosome. To identify a site on a chromosome, four items are required: 1. Chromosome number 2. Arm designation 3. Region number 4. Band number

Answer 52

Use cells in metaphase typically Use cells in prometaphase for high resolution Called a karyotype when chromomes put into an ordered arrangement. 1. Use **phytohemagglutinin (PHA)** to include 2. Use **colchicine** to stop cells in metaphase

Answer 53

* Used to ID **structurally abnormal chromosomes** * Can **quantify a specific number of copies** of a specific DNA segment * Often used after chorionic villus sampling (CVS) or amniocentesis * To determine the # of chromosomes 21, 13, 18, X, and Y * Effective to ID **microdeletions** * Need to know what you are looking for

Answer 54

* Used as **first-tier testing** in patients who do not fit a specifically known syndrome * Can identify copy number changes * _Detects_ **unbalanced** chromosomal changes **(gains/losses)** * _Does not detect_ **balanced** structural changes **(translocations and inversions)** * Clinical interpretation can be complicated

Answer 55

**Numerical anomalies** ⇒ abnormal number of chromosomes per cell **Structural aberrations** ⇒ a change in the molecular organization of the chromosome. Can be balanced or unbalanced

Answer 56

**The gain or loss of one or more chromosomes.** Results from **nondisjunction** or **anaphage lag** during mitosis or meiosis. Cell does not contain an integral multiple of 23 chromosomes.

Answer 57

A structural chromosomal abnormality with **no net change in essential genetic material.** Usually a normal phenotype.

Answer 58

A structural chromosomal abnormality with a **gain or loss of essential genetic material**.

Answer 59

A piece of one chromosome becomes inappropriately attached to another. The resulting chromosomes are called **derivatives** (der).

Answer 60

Involves breaks in two different chromosomes with **mutual interchang**e and **no apparent loss of chromosomal materia**l. If no critical material is lost, it is a balanced translocation. Ex. **Philadelphia chromosome** and **chronic myeloid leukemia (CML)**

Answer 61

The union of the **long arms** of **two acrocentric chromosomes** at the centromeres. Loss of the repetitive copies of ribosomal RNA in short arms **does not constitute a loss of critical DNA**. Are initially **balanced**. May result in monosomy or trisomy following gametogenesis ⇒ form unbalanced gametes

Answer 62

A piece of chromosome breaks off, does not reattach to any chromosome, and becomes lost in the cell. A **partial monosomy** for the deleted region can result. Clinical impact varied based on affected genes. _Two types:_ **Deletion** ⇒ visible loss of chromosomal material that can be detected by traditional metaphase banding. **Microdeletion** ⇒ loss of a smaller amount of chromosomal material only visible with high resolution banding or FISH. Associated syndromes referred to as **continuous/contiguous gene syndromes**.

Answer 63

When a single chromosome breaks and a piece of that chromosome is reinserted elsewhere

Answer 64

When a segment of a chromosome is copied and then inserted back into the chromosome resulting in multiple copies.

Answer 65

When a chromosome has two breaks liberating a piece that flips upside down and reinserts into the same chromosome. Most are balanced rearrangements.

Answer 66

Chromosome that is missing 1 arm (either p or q) and have a second copy of the remaining arm.

Answer 67

* p ⇒ short arm * q⇒ long arm * - ⇒ missing * + ⇒ additional * t ⇒ translocation * inv ⇒ inversion * dup ⇒ duplication * del ⇒ deletion * / ⇒ seperates two distinct cell lines (e.g. mosaicism)

Answer 68

Chromosomal change with 69 chromosomes (3n). Usually results in spontaneous abortion. Caused by dispermy, digyny, diandry, mosaicism.

Answer 69

Fertilization of a haploid egg by two haploid sperms.

Answer 70

Fertilization of a diploid egg due to maternal nondisjunction by a haploid sperm.

Answer 71

Fertilization of a haploid egg by a diploid sperm due to paternal nondisjunction.

Answer 72

Complex phenotypes apparently resulting from the disturbance of two or more unrelated genes in a chromosomal region to produce a consistent and recognizable phenotype. Usually detected by FISH or CMA.f

Answer 73

Used to confirm or rule out a know or suspected genetic disorder in a symptomatic individual.

Answer 74

Testing of an **asymptomatic** individual with a family history of a genetic disorder. Two types: 1. **Presymptomatic** ⇒ eventual development of symptoms is certain when the gene mutation is present 2. **Predispositional** ⇒ eventual development of symptoms is likely but not certain when the gene mutation is present

Answer 75

Peformed to identify individuals who carry one copy of a gene mutation. Can be offered as part of: * As part of universal screening protochols for diseases such as CF or spinal muscular atrophy * As indicated by population screening * Ex. Tay Sachs in Ashkenazi Jews or Irish decent

Answer 76

Performed very early following in vitro fertilization. New techniques biopsy and anlyze the polar bodies. Offered to couples with high change of having a child with a serious disorder.

Answer 77

Performed during pregnancy to asses health status of embryo or fetus. Available to all pregnant women in US. Includes US, maternal serum screening, cell-free DNA (cfDNA) analysis of maternal blood, amniocentesis, chorionic villus sampling.

Answer 78

Done shortly after birth to identify serious genetic conditions so treatment can be started asap. Mandatory in the US.

Answer 79

Birth defect with a major functional or cosmetic significance.

Answer 80

Birth defect that poses no significant functional, health, or cosmetic burden.

Answer 81

Trait present at birth that includes mild variations seen in the population.

Answer 82

An anomaly affecting a single body site. Can be inherited in a defined manner but most have multifactorial cause.

Answer 83

Two or more unrelated major structural defects occuring in a single child. A **pattern** might exist ⇒ a combination of anomalies or dysmorphologies found together in an individual.

Answer 84

A group of well-characterized major and minor anomalites (freatures) that are commonly found together due to a single etiology.

Answer 85

A group of malformations occuring together more often than one would expect based on their individual frequencies but does not have a predictable pattern of recognition and/or a suspected underlying ethiology. Can be a manifestation of several recognized disorders rather than a distinct anatomic or etiologic entity.

Answer 86

A pattern of anomalies derived from a single known defect or mechanical factor, which may have multiple etiologies. May produce multiple secondary and tertiary anomalies in a cascading fashion.

Answer 87

Disturbances in the developmental field organization or communication of specifc cells in the embryo results in a pattern of anomalies.

Answer 88

Type of developmental field defect caused by inadequate neural crest contributions to the embryonic pharyngeal pouches. Caused by a microdeletion at 22q11. CATCH-22: **C**ardiac abnormalitiy **A**bnormal facies **T**hymic aplasia **C**left palate **H**ypocalcemia/**H**ypoparathyroidism Chromosome **22**

Answer 89

Any defect resulting from an error in morphogenesis or an intrinsically abnormal developmental process. "Abnormal from the beginning."

Answer 90

An anomaly caused by in utero desctruction of a previously normally formed structure. Can be caused by physical forces, vascular disruptions or clots, and teratogens. "Started out normal but was destroyed."

Answer 91

An anomaly involving the change in size or shape of an anatomic structure due to mechanical forces that distort an otherwise normal structure. Generally not caused by a chromosome or single gene abnormality. "Started out normal then altered but still there."

Answer 92

A dysmorphic deffect caused by the abnormal organization or functional of a specific tissue type throughout the body. Often due to a single gene disorder that impacts embryogenesis.

Answer 93

SNPs in the **Methylene Tetrahydrofolate Reductase (MTHFR)** gene can significantly decrease the effectiveness of normal folic acid supplementation. Expecting mothers need to take bioactive form of folic acid instead.

Answer 94

A toxin, drug, infectious agent, physical condition, or deficiency where in utero exposure can alter fetal morphology or function.

Answer 95

1. Need for maternal exposure 2. Nature of the agent * Determines the mechanism of transport and action 3. Existence of a critical window of exposure 4. Dose-related response 5. Maternal and embryo genotypes 6. Consistent deviation of normal development

Answer 96

A similar phenotype due to different etiology.

Answer 97

A time in prenatal development during which a particular organ or body part is most susceptible to teratogenic damage. 3-8 weeks gestation is most sensitive to teratogens.

Answer 98

Teratogenic effects only occurs once a critical dose or a threshold is exceeded.

Answer 99

The effective dose of a teratogen can be altered by the presence of other substances.

Answer 100

If taken during the critical period **21-35 days** after implantation, organogenesis during that time affected in a dose dependent fashion. Phenotypes: **Symmetrical limb reduction defects** **Heart defects** Cleft lip or palate Ear malformations w/ hearing impairment Duodenal or biliary atresia

Answer 101

* Able to **penetrate tissues** * Appears to exhibit the **"all or none"** rule * Between 2-15 weeks, there is a dose response: * microcephaly, intellectual disability, cancer * Later exposure associated with leukemia and severe intellectual disability

Answer 102

* Can result in **neural tube defects** and **growth issues** * In rare cases cause heart, abdominal wall, or oral cleft defects

Answer 103

Accounts for 2-3% of congenital anomalies. Pathogen must be able to cross the placenta. TORCH infections: _**TO**xoplasmosis_ ⇒ parasitic infection from cat feces _**R**ubella_ ⇒ worse during 1^st trimester _**C**ytomegalovirus_ (CMV) ⇒ most will not have signs or symptoms, some w/ severe microcephaly if during 1st, and hearing impairment if during last trimester _**H**erpes_ ⇒ most from lesions in birth canal

Answer 104

1. **Anticonvulsants** (ex. Dilantin) * Can lead to fetal hydration syndrome ⇒ intrauterine growth deficiencies 2. **Accutane** (isotretinoin) * Causes brain defects, hydrocephalus, heart/limb/face defects, inc spontaneous abortion 3. **Antibiotics** * Usually safe except aminoglycosides, tetracycline, and doxycycline 4. **Alcohol** * Fetal Alcohol Syndrome (FAS) * Fetal Alcohol Effect (FAE) 5. **Cigarette smoke** * Impacts blood flow to fetus

Answer 105

* **Type I and II DM** have difficulties with BGL control throughout pregnancy. * **Diabetic embryopathy** can affect any developing organ system * Hyperglycemia during 1st trimester increases risk of major malformations by 3-4 fold * **Gestational DM** develops ~ 24 weeks. * Generally do not have increased risk of malformations Try to control BGL before pregnancy and throughout gestation. Take more folic acid.

Answer 106

Traits caused by the combined effects of multiple genes/alleles at different loci. Ideally, excludes environmental influenes.

Answer 107

Includes the combined effects of multiple genes at different loci, the environment, and stochastic events.

Answer 108

1. Genes/alleles 2. Environmental exposures 3. Stochastic events

Answer 109

1. Discontinuous variation traits: * Qualitative * Ex. cleft lip, DM, schizophrenia 2. Continuous variation traits: * Quantitative * Ex. height, IQ, blood pressure

Answer 110

The genetic, environmental, and stochastic events that underlie all multifactorial disease.

Answer 111

The phenotype does not develop unless the individual crosses a threshold through the cumulative effects of genetic, environmental, and stochastic components.

Answer 112

**Empirical risks** determined by **direct observation** of prevalence in the population. Differ substantially from one population to another. * Decreases rapidly in more remotely related relatives. * If more than one close family member, recurrence risk higher in that family. * If phenotype severe, recurrence risk higher. * If trait more common in one sex, offspring of less freq. sex has a higher recurrence risk * Recurrence risk for relatives of affected person increases as population risk decreases

Answer 113

How much genetic factors play in the varibility of a specific trait in a specific population and a specific environment. Genes play no role ⇒ H²= 0 Genes completely control the trait ⇒ H²= 1 Use familial aggregation studies, twin/sibling/adoption studies for condordance and correlation, animal models.

Answer 114

Links the current high prevalence of obesity and type 2 DM to selective events in human evolution. Thought that certain advantagous genetic variants that allowed survival during periods of erratic food supply now increase risk of disease.

Exam 1 Genetics Thread Flashcards

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