THERIO - Genetic Counseling & DSD

Question 1

This law applies to all owners of dogs whether they intend to breed them or not and includes the need for:
- suitable environment and diet
- to be housed with/apart from other dogs
- to be able to exhibit normal behavior
- to be protected from pain, injury, suffering, and disease

Answer 1

Animal Welfare Act, 2006

Question 2

Why is the genetic diversity of each breed considered finite?

Answer 2

All the useful genetic variation of each breed is in the dogs that founded the breed.

Question 3

In each generation, alleles can be lost by ___ or due to ___.

Answer 3

In each generation alleles can be lost by genetic drift or due to the breeder phenotypic selection.

Question 4

Promoting a specific gene means promoting ____ because of the gene’s linkage.

Answer 4

Promoting a specific gene means promoting a series of genes because of the gene’s linkage.

Question 5

Often _____ is necessary to manifest a phenotype, but breeding for this means ___.

Answer 5

Often homozygosity is needed for manifesting a phenotype, but breeding for this means killing the immune system.

Question 6

Six consequences of homozygosity/inbreeding:

Answer 6

Decreased fertility
Difficulty whelping
Smaller litters
Higher puppy mortality
Puppies that don’t thrive
Shorter lifespan

Question 7

If mated, genetically healthy dogs should ___.
Animals that cannot produce viable offspring are removed by ___.

Answer 7

If mated, genetically healthy dogs should get pregnant.
Animals that cannot produce viable offspring are removed by natural selection.

Question 8

The only way to improve the genetic health of the breed is to ___.

Answer 8

The only way to improve the genetic health of the breed is to manage the health of the breed’s gene pool.

Question 9

How might a previously rare mutation become common?

Answer 9

Creating many puppies from the favorite sire makes dozens of copies of all the bad alleles in that dog - which were never a problem before because they were recessive.

Question 10

Phenotype depends on __ and ___.

Answer 10

Phenotype depends on genetics and environment.

Question 11

What is EBV?

Many inherited diseases cannot be controlled by a simple DNA test because:

Answer 11

Estimated Breeding Value
An EBV for a complex inherited disease is a calculation of risk of disease based on pedigree information and the results of a physical test of both parents.

Many inherited diseases are caused by multiple genes and environmental factors and therefore cannot be controlled by a simple DNA test.

Question 12

FCI International Breeding Strategies

To reduce inbreeding, no dog should have more offspring than equivalent to ___.

Answer 12

5% of the number of puppies registered in the breed population during a five-year period

Question 13

What is heritability?

What does heritability measure?

Answer 13

Heritability is the proportion of variance in a particular trait, in a particular population, that is due to genetic factors as opposed to environmental influences or stochastic variation.

Heritability measures the fraction of phenotype variability that can be attributed to genetic variation.

Question 14

SLIDE 19, 20

Question 15

Examples of heritable traits in dogs:

Answer 15

Athletic performance
Coat color
Olfactory
Size and shape

Question 16

Examples of heritable disorders in dogs:

Answer 16

Cleft palate
Umbilical hernia
Cryptorchidism
PDA
Hip dysplasia
Immunodeficiency
Coagulopathy
Brachygnathism
Mucopolysaccharidosis
Entropion

Question 17

Single-minded focus on elimination of one genetic defect can lead to:

Answer 17

Diminishing genetic diversity and increased occurrence of other defects

Question 18

Selection of breeding animals should be based on:
(5)

Answer 18

Goals
Health
Conformation
Performance
Behavior

Question 19

What is required by the AKC for frequently used sires and for all chilled and frozen semen breeding?

Answer 19

DNA parentage profiling

Question 20

SLIDES 35-37

Question 21

Disorders of sexual develop are reproductive anomalies that can be due to these three types of abnormalities:

Answer 21

Chromosomal
Gonadal
Phenotypical

Question 22

Chromosomal abnormalities result from:

In general, affected individuals:

Answer 22

Chromosomal abnormalities result from non-disjunction errors during meiosis.

In general, affected individuals:
- have undeveloped genitalia
- are infertile
- with external phenotype as male or female (???)

Question 23

Trisomy XXY Syndrome (Klinefelter in people)

____ XXY dog, ____ XXY cat
Most males have ______ testes, epididymides, and vas differentia.
External genitalia vary from ______ to ______.
How is the complete male phenotype explained?
What prevents normal spermatogenesis?

Answer 23

Trisomy XXY Syndrome (Klinefelter in people)

79 XXY dog, 39 XXY cat
Most males have HYPOPLASTIC testes, epididymides, and vas differentia.
External genitalia vary from HYPOPLASTIC to NORMAL.
Complete male phenotype is explained by the presence of testes capable of producing MIS
Presence of two X chromosomes prevents normal spermatogenesis

Question 24

Calico Cats

Gene for orange and non-orange (black/brown) are ______ at the orange locus.
_____ females can express any combination of colors due to random inactivation of _____ and can have random patches of tortoise shell or calico.
Normal males should only be able to express the _____ or ____ coat.
Calico males are XXY, XX/XXY, XY/XXY, or other _____ combinations.

Answer 24

Gene for orange and non-orange (black/brown) are X-LINKED ALLELES at the orange locus.

NORMAL HETEROZYGOTE females can express any combination of colors due to random inactivation of ONE OF THE X CHROMOSOMES and can have random patches of tortoise shell or calico.

Normal males should only be able to express the ORANGE or NON-ORANGE (BROWN/BLACK) coat.

Calico male cats are XXY, XX/XXY, XY/XXY, or other CHIMERIC/MOSAIC combinations.

Question 25

Monopsony XO Syndrome (Turner in humans)

Reported in what species?
General phenotype:
Externally ____ phenotype
Genitalia:
Gonads:
Cases in the bitch reported:

Answer 25

Reported in horses, dogs, cats, alpacas, llamas
General phenotype small or normal stature
Eternally female phenotype
Infantile female internal genitalia
Gonadal dysgenesis (streak gonads)
Cases in the bitch reported hyperestrogenism, swollen vulva, serosanguinous discharge, enlarged clitoris

Question 26

Chimerism results from ___.

Answer 26

The fusion of two zygotes (XX/XY)

Question 27

Chimera with testes:

Genitalia:
Urinary:
Penis, abdominal testis, uterus:

Answer 27

Ambiguous genetalia: cranially displaced vulva, enlarged clitoris or small prepuce
Dysuria and urine scalding may be present
Hypoplastic penis, abdominal testis, uterus

Question 28

XX/XY Freemartinism

What is it?
Species?
Ovaries:
External vulvar region:

Answer 28

Female born to co-twin to a male
Common in cattle but has been described in sheep, goats, camels, deer, big horn sheep
Ovaries of the freemartin do not develop normally and remain very small
The external vulvar region can range from normal looking female to a male-like appearance

Question 29

What is sex reversal?

XX true hermaphrodites have ____
XX males have _____
XX Sry-negative males have been described in ____.

Answer 29

The gonadal sex does not agree with the chromosomal sex

XX true hermaphrodites have ovotestes
XX males have bilateral testes
XX Sry-negative males have been described in goats, pigs, camelid, horses, and dogs. In goats and pigs it is described as an inherited autosomal recessive syndrome.

Question 30

In dogs, XX sex reversal is inherited as an autosomal recessive trait in ____ and possibly ___.

In dogs, XX with ovotestes or XX with testes, the degree of masculinization depends on ____.

Answer 30

In dogs, XX sex reversal is inherited as an autosomal recessive trait in AMERICAN COCKER SPANIELS and possibly GERMAN SHORTHAIRED POINTER.

In dogs, XX with ovotestes or XX with testes, the degree of masculinization depends on THE DEGREE OF GONADAL FUNCTION.

Question 31

Goats

XX reversal (_____________) linked to the polled trait and functional deletion of Pisrt1 and FoxL2 genes proposed to be _____ genes.

Loss of these genes leads to ____ in XX homozygous PIS -/- mutants.

Functionally ____ is present.

Failure of complete ______ suggests insensitivity of target organ to MIS.

Bucks with ______.

Answer 31

Goats

XX reversal (POLLED INTERSEX SYNDROME) linked to the polled trait and functional deletion of Pisrt1 and FoxL2 genes proposed to be OVARY-DIFFERENTIATING genes.

Loss of these genes leads to TESTIS FORMATION in XX homozygous PIS -/- mutants.

Functionally MIS is present.

Failure of complete MULLERIAN DUCT REGRESSION suggests insensitivity of the target organ to MIS.

Bucks with GYNECTOMASTIA.

Question 32

With phenotypical abnormalities, the ______ are in agreement, but the ______ is different.

Four examples:

Answer 32

With phenotypical abnormalities, the CHROMOSOMAL AND GONADAL SEX are in agreement, but the PHENOTYPIC SEX is different.

• male/female pseudohermaphtoditism
• persistent Mullerian Duct Syndrome
• defects in androgen-dependent masculinization

Question 33

Female pseudohermaphroditism results from ____.

X-linked mutation of Dax1 leading to ________.

Iatrogenic exposure of the fetus to ________.

XX ____, ______ and masculinized _____.

Answer 33

Female pseudohermaphroditism results from VIRILIZING EFFECTS OF ENDOGENOUS IN-UTERO ANDROGEN EXPOSURE.

X-linked mutation of Dax1 leading to CONGENITAL ADRENAL HYPERPLASIA.

Iatrogenic exposure of the fetus to androgens or progestagens during gestation.

XX karyotype, ovaries and masculinized internal or external genetalia

Question 34

Male pseudohermaphroditism

XY ______, _______ but the internal and/or external genitalia present variable degrees of __________.

Failure of ______ or defects in ________.

Answer 34

Male pseudohermaphroditism

XY karyotype, testes but internal and/or external genitalia present variable degrees of feminization

Failure of regression of Müllerian ducts or defects in androgen dependent masculinization

Question 35

This is reported as an inherited autosomal recessive trait in the miniature schnauzer. They secrete bioacive MIS but the ______ seem to be insensitive possibly due to a defect in MIS receptor.

Answer 35

Persistent Mullerian Duct Syndrome

Müllerian ducts insensitive possibly due to a defect in MIS receptor

Question 36

Persistent Mullerian Duct Syndrome

Dogs are XY with ______ but ________.
Dogs have normal genitalia but also ______.
When does dx usually occur?
Treatment:

Answer 36

Dogs are XY with testicles but cryptorchid
Normal genitalia but also uterus, oviducts, cervix and cranial vagina
If testes are descended the DX usually occurs when they develop pyometra, urethral disease, or prostatic problems
Treatment: castration and removal of Müllerian ducts

Question 37

Defects in androgen production vs androgen excess

Answer 37

Defects in androgen production
Karyotype normal, T2 level normal, carrier females are fertile
Conversion of T2 in DHT defect
Defect of 5a-reductase type 2 isoenzyme has been shown to be inherited as an autosomal recessive pattern
Defects in androgen receptor: testicular feminization, XY males with testes but with total or partial failure of masculinization of internal and external genetalia

Androgen excess
XX with ovaries but with ambiguous genitalia due to androgen exposure during development
Due to fetal or maternal origin
- fetal: 11 beta hydroxylase deficiency reported in calico cats
- maternal: androgens and progestagens administered to dam during pregnancy
DX: STIM test or ACTH STIM test

Question 38

Cryptorchidism

Associated with ______ or can be isolated.
Testes should be completely descended by _____ of age in dogs and cats, but some are slower to descend.
Considered cryptorchid if testes are not in the scrotum by _______.

Answer 38

Cryptorchidism

Associated with XX DSD
5 days
6 months

Question 39

What is hypospadia?
What breed may have a familial basis?

Answer 39

Abnormal location of the urinary orifice with incomplete masculinization of the urogenital sinus (closure of the urethra).
The location of the urethra can vary from the centrum of the glans penis, the penile shaft, the penoscrotal junction, the scrotum, or the perineum.

May have a familial basis in Boston terriers.

Question 40

This defect of genital tract development is associated with renal a genesis in alpacas.

Answer 40

Testicular agenesis/Anorchism/monorchism

Question 41

Name three other common defects of genital tract development in males

Answer 41

Persistent frenulum - possibly inherited
Testicular hypoplasia - some evidence of inheritance
Segmental aplasia of the epididymes / ductus deferens (spermatocele, cysts)

Question 42

Other common defects of genital tract development in females

Answer 42

Persistent hymen
Vaginal/cervical aplasia
Double vagina and/or cervix
Segmental aplasia of the uterus (uterus unicornis) and/or uterine tubes
Ovarian digenesis/hypoplasia/dysgenesis
Müllerian duct agenesis - cats/dogs often have associated unilateral renal agenesis