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30 May, 14:00

A couple planning their family are aware that through the past three generations on the husband's side a substantial number of stillbirths have occurred, and several malformed babies were born who died early in childhood. The wife has studied genetics and urges her husband to visit a genetic counseling clinic, where a complete karyotype-banding analysis is performed. Although the tests show that he has a normal complement of 46 chromosomes, banding analysis reveals that one member of the chromosome 1 pair (in group A) contains an inversion covering 70 percent of its length. The homolog of chromosome 1 and all other chromosomes show the normal banding sequence. lal How would you explain the high incidence of past stillbirths? ib) What can you predict about the probability of abnormality / normality of their future children? (c) Would you advise the woman that she will have to bring each pregnancy to term to determine whether the fetus is normal? If not, what else can you suggest?

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  1. 30 May, 16:42
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    a) There are lots of genes on chromosome 1 could be affected, and the gametes could be imbalanced (missing segments of DNA or whole chromosomes)

    b) Roughly 50%

    c) No. I would advise that the couple undergo preimplantation genetic diagnosis, so that a zygote carrying the normal copy of chromosome 1 could be selected.

    Explanation:

    Chromosome 1 is one of the largest and most gene rich chromosomes. An inversion that covers 70% of its length would cover lots of genes.

    While an inversion on its own would not seem problematic (as all the genes on the chromosome are still there), when it comes to meiosis, the sister chromatids would not be able to correctly align, and crossing over would further complicate this. It could also lead to unbalanced gametes missing entire parts of the chromosome. Therefore, there are likely numerous genes that will be affected and messed up by the inversion.

    This could explain the high incidence of past still births, as if lots of genes are affected, and non-functional, the pregnancy would be rendered non-viable, or highly deleterious causing premature death.

    b) There is a 50% chance of a child inheriting the defective copy of chromosome 1 (and 50% of a chance of them inheriting the normal chromosome 1. Therefore, there is likely a 50% chance that future offspring would be affected by defects

    c) No. I would advise that the couple undergo preimplantation genetic diagnosis. In this, the couple undergoes in vitro fertilization (IVF). When embryos are produced through IVF, they can then be tested for the presence of the abnormal chromosome. Embryos will only be implanted into the mother if the normal chromosome 1 is present.
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