Genetics and Bio-informatics CIA:1(B) 1

Pedigree Chart Analysis

Kamya Sridharan, 20214044

Department of Social Sciences and Humanities

Genetics and Bioinformatics BPSY461N

Mr Priyesh C.

25 January 2022
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Pedigree chart analysis

Case Identification and Details

The case taken is of a genetic disorder called congenital non-goitrous hypothyroidism-4

(CHNG4) or simply hypothyroidism for short. This disorder has an autosomal recessive

inheritance pattern (Pradhan et al, 2011). In technical terms, Congenital hypothyroidism is

characterized by a permanent thyroid (an important hormone gland) deficiency present at birth

and resulting from a deficiency in TSH synthesis that has_material_basis_in homozygous

mutation in the TSHB gene on chromosome 1p13 (Hahn Jr, 1975). The symptoms mainly

include predominantly fatigue and weight gain. Metabolism continues to slow, there is an

increased sensitivity to cold, constipation, dry skin, puffy face, hoarseness, muscle weakness,

elevated blood cholesterol level, muscle aches, tenderness and stiffness, pain, stiffness or

swelling in your joints, heavier than normal or irregular menstrual periods, thinning hair, slowed

heart rate and even depression and impaired memory. In infants, this may present as excessive

sleeping, poor muscle tone, large protruding tongue and difficulty breathing.

One such case is patient X who noticed her low thyroid levels and abnormally high TSH

(thyroid-stimulating hormone) in a blood test and was thus diagnosed with hypothyroidism. She

was already experiencing some of the symptoms like fatigue, low metabolism, weight gain,

irregular periods and was able to attribute hypothyroidism as the cause. Some members of her

family are experiencing the same disorder and thus a pedigree chart helped lay down the

inheritance pattern of the same.

Pedigree Chart
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If we assume the allele of hypothyroidism is H (dominant) and h (recessive), the diseased

case must possess hh pair of alleles since the disorder is of the autosomal recessive pattern.

In the above pedigree chart depicting the inheritance pattern of hypothyroidism, four

generations of a family are represented. Below is the analysis of each generation with respect to

their inheritance pattern:

Generation I: All the members of this generation are deceased. Parents 1 and 2 are

considered to be heterozygous (Hh) carriers as their child in generation II is an affected

offspring. The offspring must receive recessive h allele from both parents, and since neither

parent was affected, it is concluded that parents are heterozygous carriers. Parent 3 is assumed to
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be a carrier in this chart as their 6th offspring is most likely a carrier too. (Although parent 4

could also be the carrier).

Generation II: In this generation, parent 1 is affected by the disease and has hh genotypic

expression. Other offsprings have normal expressions except 6. Parents 5 and 6 are having

heterozygous hh genotypic expression as their offspring (3) in generation III is an affected child.

Generation III: Parent 2 is a heterozygous carrier (Hh) and parent 3 is an affected parent

(hh). All other members are unaffected.

Generation IV: both offsprings are affected and show phenotypic expression of the

disease. If parents 2 and 3 from generation III decide to have more children, their offsprings will

either be carriers or affected. Patient X represents offspring 1 in generation IV

It is clear from the pedigree chart that hypothyroidism is an autosomal (affecting both

males and females) recessive (not expressed in every generation) genetic disorder. The below

diagram shows the pedigree chart and the possible genotypic expressions:
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The genotypic expression of HH indicates that the individual is unaffected, Hh indicates a

carrier and hh indicates affected individual.

Conclusion and discussions

This pedigree chart helped us to discover that any offsprings of parents 2 and 3 of

generation III will have the recessive allele, hence they will either be affected or will be carriers.

Another intriguing phenomenon is that only female members of the family have been affected

even though autosomal disorders are not discriminatory when it comes to gender.

The genotypic expressions of generations III and IV were relatively more clear than

generation I and II, this is due to the variable expressivity of the genotype. Analysis of various

generations needs to be done so the most accurate inheritance pattern is discovered. This shows

the importance of maintaining health records and taking regular blood tests to predict the future

of offsprings.
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References

Hahn Jr, H. B. (1975). Congenital Nongoitrous Hypothyroidism. Postgraduate medicine, 57(7),

71-74.

Pradhan, S., Sengupta, M., Dutta, A., Bhattacharyya, K., Bag, S., Dutta, C., Ray, K. (2011):

Indian Genetic Disease Database. Nucleic Acids Res. 39 (suppl 1): D933-D938 DOI:

10.1093/nar/gkq1025