Chromosomal & genetic syndrome

What is it? And Classification Genetic Syndrome

Its effect on animal reproduction and Production Effects on Animal Breeding

Detection of Chromosomal Abnormality Detection of chromosomal abnormality

Genetic SyndromeSyndrome- set of signs and symptoms

characterized by malformations or malfunctions in any of the body’s systems

3 Groups of genetic diseases

1. Disorders with multifactorial inheritance (polygenic)

2. Monogenic (mendelian) disorders

3. Chromosomal aberrations

How abnormality happen?Typically occur when there is an error in cell

division following meiosis or mitosisMistake in egg cell or sperm

Anomaly present in every cell of body

Some anomaly after conceptionMosaicism

Disorders with multifactorial inheritance (polygenic)influence of multiple genes +

environmental factorsrelatively frequentEx.

Diabetes mellitus Hypertension Gout Schizophrenia Congenital heart disease - certain forms Some types of cancer (ovarian, breast, colon)

Monogenic (mendelian) disorders

mutation of 1 gene, mendelian type of inheritances

1. Autosomal dominant

2. Autosomal recessive

3. X-linked

Autosomal dominant disordersboth homozygotes and heterozygotes are

affected

usually heterozygotes (inherited from one parent)

both males and females are affected

transmission from one generation to the other

50% of children are affected

Ex.

Familial hypercholesterolemia Marfan syndrome Ehlers-Danlos syndrome

Autosomal recessiveonly homozygotes are affected, heterozygotes

(parents) are only carriers

25% of descendants are affected

if the mutant gene occurs with low frequency - high

probability in consanguineous marriagesonset of symptoms often in childhood

frequently enzymatic defect

testing of parents and amnial cells

Ex.

Cystic fibrosis Phenylketonuria (PKU) Galactosemia Glycogen storage diseases (glycogenoses) Lysosomal storage diseases Gaucher disease

X-linked diseasestransmitted by heterozygous mother to sons

daughters - 50% carriers, 50% healthy

sons - 50% diseased, 50% healthy

Children of diseased father - sons are healthy, all daughters are carriers

Hemophilia A (defect of Factor VIII) Hemophilia B (defect of Factor IX) Muscle dystrophy (Duchen disease)

Types of Chromosomal aberrations

Numerical AbnormalityNormal- Two copies (2n) of the same

genome in somatic cell

Aberration- deviation from diploid (2n )

Types

Aneuploidy

Term Chromosomes DescriptionAneuploidy 2n+/- few One or few chromosome extra or

missingTrisomy 2n+1 One extra chromosomeDouble trisomy

2n+1+1 Two non-homologous chromosome extra

Tetrasomic 2n+2 One chromosome pair extraMonosomic 2n-1 One chromosome missingDouble monosomic

2n-1-1 Two non-homologous chromosome missing

Nullisomy 2n-2 One pair of homologous chromosome missing

Syndrome

Karyotype Main clinical features

Down Trisomy 21 Short, broad hands with single palmar crease, decreased muscle tone, mentalretardation, broad head with characteristic features, open mouth with large tongue,up-slanting eyes

Edwards Trisomy 18 Multiple congenital malformations of many organs, low-set malformed ears, recedingmandible, small eyes, mouth and nose with general elfin appearance, severe mentaldeficiency, congenital heart defects, horseshoe or double kidney, short sternum,posterior heel prominence

Patau Trisomy 13 Severe mental deficiency, small eyes, cleft lip and/or palate, extra fingers and toes,cardiac anomalies, midline brain anomalies, genitourinary abnormalities

Turner 45,X Female with retarded sexual development, usually sterile, short stature, webbing of skinin neck region, cardiovascular abnormalities, hearing impairment, normal intelligence

Klinefelter

47,XXY Male, infertile with small testes, may have some breast development, tall, mild mentaldeficiency, long limbs, at risk for educational problems

Triple X 47,XXX Female with normal genitalia and fertility, at risk for educational and emotionalproblems, early menopause

XYY 47,XYY Tall male with normal physical/sexual development, normal intelligence, increasedtendency for behavioural and psychological problems

EuploidyTerm Chromosom

eDescription

EuploidMonoploid X Only one genome presentHaploid n Gametic chromosome number of the

concerned species presentPolyploid More than two copies of genomeAutopolyploid More than two copies of the same

genome presentAutotriploid 3X Three copies of the same genome

presentAutotetraploid

4X Four copies of the same genome present

Allopolyploid Two or more distinct genome; generally each genome has two copies

allotetraploid 2X1+2X2 Two distinct genomes; generally each genome has two copies

Structural abnormality

Chromosome BreakageCause – not definitely knownPossible factor-cosmic radiation, nutritional

deficiency, environmental condition

type

Deficiency or deletion

Loss of chromosome segment

Loss of chromosome segment has a deleterious effect and larger deletion may be lethal

Ex. Cri du chat syndrome

Cry of the cat in French deletion of short arm of chromosome 5 Baby make high pitch cries Wide set eyes, small head and jaw, mentally retarded

Duplication or Repeat(presence of additional chromosome segment)

Not produce as drastic effect as deletion in term of phenotype and survival

Syndrome Chromosome region duplicated

Main clinical features

Beckwith–Wiedemann

11p15.5 Large tongue, tissue and organ overgrowth, mild mental retardation

Charcot–Marie–Toothdisease type 1A

17p11.2-p12 Decreased reflexes, progressive distal muscular wasting, decreasedmuscle tone, sensory neuropathy

Cat-eye 22pter-q11.2 Eye defects, absence of anal opening, skin tags in front of ears,characteristic facies, renal, skeletal and genital anomalies, mentalretardation

Inversion

Inversion suppresses genetic recombinations.

Helpful in maintaining hetrogygosity and balanced lethal system

The most common inversion seen in humans is on chromosome 9, at inv(9)(p12q13)

Translocation(a segment from one chromosome is detached and

reattached to a different – non homologous

chromosome)Gene from one chromosome is transferred to

another

Simple Translocation - One sided translocation

Reciprocal Translocation- mutual exchange of segment

Ring FormationA portion of a chromosome has broken off

and form a circle or ringCan happen with or without loss of genetic

material

Detection of chromosomal abnormalityBy Karyotyping Chromosome Banding- G, Q, C, R banding

etc.FISH (fluorescent in situ hybridization)Comparative genome hybridization (CGH)SNP (single nucleotide polymorphism)

microarraysComparative genome hybridization (CGH)

Effects on Animal Breeding

Disorder of sex development (DSD)

Impaired fertililty

Disorder of sex development cytogenetic analysis focuses on the

identification of sex chromosomesXX/XY chimerism-

Freemartinism, observed in females originating from heterosexual pregnancies, Infertile

Sex chromosome aneuploidiesdeleterious effects on sex developmentsterility

Mutation The most common clinical features

Effects on fertility

Decreasing incidence in different species

X monosomy

Usually normal external genitalia; abnormal oestrus or no clinical signs of oestrus; small or hypoplastic ovaries

Sterility Horse > cat and dog > cattle and pig

XXX trisomy

Normal external genitalia; usually lack of clinical signs, sometimes irregular oestrus

Infertility Dog, horse

XXY trisomy

Small and hypoplastic testes; abnormal spermatogenesis (oligospermia or azoospermia)

Sterility Cat and cattle > dog and horse > pig

XYY trisomy Usually normal phenotype; small testes

Infertility Cattle

Decreased fertility in carriers of balanced chromosome aberrations

Balanced structural rearrangements Robertsonian translocation ,tandem fusions, reciprocal translocations inversions

are inheritable mutationsNo visible alteration of sex development

Genetically abnormal animalsGenetically abnormal animals

Partial Hypotrichosis Complete Hypotrichosis

congenital alopecia and anaemia presence of marked wrinkling of the skin

AIChromosomally abnormal bull

Use of chromosomally

abnormal semenInfertility, repeat breeding, genetic

disorder

Huge disaster

Dead and live sperm, sperm motility, semen

volume

SolutionGenetic

testing of animal

MATING WITHOUT TESTING

NS WITH CARRIER     BULL

AFTER GENETIC TESTING                 

AFETR GENETIC TESTINGAFETR GENETIC TESTING

GENETICALLY CLEAN POPULATION

Consequences

BLAD (Bovine Leukocyte Adhesion Deficiency). It was estimated that 16,000 calves were born with BLAD each year. Hence, the average economic loss per calf was roughly 300 US dollors.

Prevalence of BLAD in Indian HF crossbred cattle population is an alarming situation due to consistent reports from 1999 to 2013.

Factor XI deficiency (FXID) is responsible for repeat breeding in carriers leading to the financial losses . In Turkey (Akyuz et al., 2012) reported an extra $ 324 financial loss compared with a normally fertile cow due to this syndrome.

CVM ( Complex Vertebral Malformation ) carriers in India and worldwide much more higher than other four disorders i.e. BLAD, DUMPS, Citrullinemia and Factor XI

In 2012 in New Zealand Livestock Improvement Corporation (LIC) , a farmer cooperative that sells bull semen was been warned for supplying defective semen to farmers who produced 1500 defective calves with genetic defect leading to excessive hairiness and intolerance to heat ultimately reducing milk producing ability.

1;29 CFT in Jersey cross cow in Chennai (Thiagarajan et al., 1990)1;29 CFT in Jersey cross bull in MS used through AI for 9 years (Chauhan

et al.2009) 7;16 CFT in HF cross bull under use through AI in KDC Mumbai

( Biotech lab report 1999-2000)7;16 CFT in HF cross bull before use through AI in MS (Patel,1999)1;9 CFTs in Gir bull in Gujarat State ( Paderi et al., 2011b)16;20 CFT in Deoni bull calf in 16;20 in Karanataka State ( Paderi et al.,

2011a)8;29 CFT in one Gaolao Bull and it’s 12 progeny in MS ( Umrikar et al.,

2013)

CFT- Centric Fusion Translocation (Robertsonian Translocation)

References https://www.britannica.com/science/chromosomal-disorderhttps://www.genome.gov/11508982/Gene VGenetic by Dr Vijay KumarChromosome Abnormalities in Domestic Animals as Causes of

Disorders of Sex Development or Impaired Fertility http://dx.doi.org/10.5772/62053

Gholap P.N., Genetic Diseases in Cattle: A Review, Research Journal of Animal, Veterinary and Fishery Sciences Vol. 2(2), 24-33, February (2014)

Arcangelo Gentile, Inherited disorder of Cattle; A selected review, Slov Vet Res 2006;43(1)17-29